Gastrointestinal treatment system including a vibrating capsule, and method of use thereof

ABSTRACT

A gastrointestinal treatment system including a gastrointestinal capsule adapted to treat a subject following ingestion of the gastrointestinal capsule. The gastrointestinal capsule includes: (a) a housing; (b) a vibrating agitator, powered by the battery, the vibrating agitator adapted such that, in a first vibrating mode of operation, the housing exerts vibrations on an environment surrounding the capsule; (c) a power supply disposed within the housing and adapted to power the vibrating agitator; and (d) a controller adapted, in response to receipt of an activation input, to activate the vibrating agitator to operate in the first vibrating mode of operation at at least one predetermined time of day. The system and method may be used to treat an ailment of the gastrointestinal tract and/or to mitigate at least one symptom of jetlag in a subject travelling from an origin location to a destination location.

FIELD OF THE INVENTION

The present invention relates in general to gastrointestinal treatmentsystems including one or more vibrating capsules, and to methods of usethereof, and more particularly, to gastrointestinal treatment systemsand methods in which the one or more capsules vibrate, or are adapted tovibrate, at one or more specific times of day. The present inventionfurther relates in general to a method and a system for mitigating atleast one effect of jetlag, and specifically to a method for mitigatingjetlag using a gastrointestinal treatment system including one or morevibrating capsules.

SUMMARY OF THE INVENTION

In accordance with an embodiment of the present invention, there isprovided a gastrointestinal treatment system including agastrointestinal capsule adapted to treat a gastrointestinal tract of asubject following ingestion of the gastrointestinal capsule, thegastrointestinal capsule including:

(a) a housing;(b) a vibrating agitator adapted such that, in a first vibrating mode ofoperation, the housing exerts vibrations on an environment surroundingthe capsule;(c) a power supply disposed within the housing and adapted to power thevibrating agitator; and(d) a controller adapted, in response to receipt of an activation input,to activate the vibrating agitator to operate in the first vibratingmode of operation at at least one predetermined time of day.

In accordance with another embodiment of the present invention, there isprovided a gastrointestinal treatment system including agastrointestinal capsule adapted to treat a gastrointestinal tract of asubject following ingestion of the gastrointestinal capsule, thegastrointestinal capsule including:

(a) a housing;(b) a vibrating agitator adapted such that, in a first vibrating mode ofoperation, the housing exerts vibrations on an environment surroundingthe capsule;(c) a power supply disposed within the housing and adapted to power thevibrating agitator; and(d) a controller adapted, when the capsule is in an operative state, toactivate the vibrating agitator to operate in the first vibrating modeof operation at at least one predetermined time of day.

In some embodiments, the capsule is adapted to be in the operative statefollowing receipt of an activation input, which transitions the capsulefrom an inoperative state to an operative state.

In some embodiments, the subject is travelling from an origin locationto a destination location, and the system is adapted to mitigate jetlagof the subject.

In some such embodiments, the controller is adapted to activate thevibrating agitator to operate in the first vibrating mode of operationat at least one predetermined time of day according to a time zone ofthe origin location.

In some such embodiments, the controller is adapted to activate thevibrating agitator to operate in the first vibrating mode of operationat at least one predetermined time of day according to a time zone ofthe destination location.

In some such embodiments, the controller is adapted to activate thevibrating agitator to operate in the first vibrating mode of operationat a first time of day of the at least one predetermined time of dayaccording to a time zone of the origin location and at a second time ofday of the at least one predetermined time of day according to a timezone of the destination location.

In some embodiments, the predetermined time of day is selected accordingto a circadian cycle of the subject.

In some embodiments, the predetermined time of day is selected accordingto a gastric pH profile of the subject.

In some embodiments, the capsule includes at least one timing mechanism,and is devoid of sensors for sensing an environment thereof.

In some embodiments, the at least one timing mechanism comprises atimer.

In some embodiments, the at least one timing mechanism comprises aclock. In some embodiments, the at least one timing mechanism isassociated with a positioning system such as GPS.

In some embodiments, the controller is adapted, in response to theactivation input, to wait a predetermined delay time, and following thepredetermined delay time, at a time coinciding with the at least onepredetermined time of day, to activate the vibrating agitator to operatein the first vibration mode of operation.

In some embodiments, the capsule further includes at least one sensoradapted to provide the activation input.

In some embodiments, the at least one sensor includes an illuminationsensor adapted to provide the activation input upon identification oftransition of the capsule from an illuminated environment to a darkenvironment.

In some embodiments, the at least one sensor includes a pressure sensoradapted to provide the activation input upon identification of pressureapplied to the capsule, which pressure is indicative of the capsulemoving through a pharynx of the subject.

In some embodiments, the at least one sensor includes a temperaturesensor adapted to provide the activation input upon identification oftransition of the capsule from an area with ambient temperature to anarea with a human body temperature.

In some embodiments, the at least one sensor includes an accelerometeradapted to provide the activation input upon identification of anactivation motion carried out by a user of the gastrointestinal capsule.

In some embodiments, the at least one sensor includes a moisture sensoradapted to provide the activation input upon identification oftransition of the capsule from a dry environment to a humid environment.

In some embodiments, the capsule further includes a timing mechanism. Insome embodiments, in response to the activation input, the controller isadapted to activate operation of the timing mechanism to track a time ofday so as to identify the at least one predetermined time of day foractivation of the vibration agitator. In some embodiments, in responseto the activation input, the controller is adapted to activate operationof the timing mechanism to wait a predetermined duration prior toactivation of vibration agitator, such that activation of the vibrationagitator occurs at the at least one predetermined time of day.

In some embodiments, the system further includes a control unit, adaptedto provide the activation input to the controller of thegastrointestinal capsule.

In some embodiments, the control unit is adapted to provide theactivation input following ingestion of the gastrointestinal capsule bythe subject. In other embodiments, the control unit is adapted toprovide the activation input prior to ingestion of the gastrointestinalcapsule by the subject.

In some embodiments, the control unit is adapted to provide to thecontroller a current time of day, and the controller is adapted tocompute a delay time from the current time of day to the at least onepredetermined time of day, and to activate the vibrating agitatorfollowing the delay time.

In some embodiments, the control unit further includes a timing device,and is adapted to provide to the capsule, as the activation input, aninput signal indicating a current time of day being the at least onepredetermined time of day, and the controller is adapted, upon receiptof the input signal, to activate the vibrating agitator to operate inthe first vibrating mode of operation.

In some embodiments, the timing mechanism associated with the controlleris a timer, and the control unit is adapted to provide to thecontroller, as the activation input, a delay time from the current timeof day to the at least one predetermined time of day, and the controlleris adapted to activate the vibrating agitator following the delay time.

In some embodiments, the current time of day is a time of day at anorigin location of the subject. In other embodiments, the current timeof day is a time of day at a destination location of the subject.

In some embodiments, the activation input includes the at least onepredetermined time of day. In some embodiments, the activation inputincludes a delay time from a current time to the at least onepredetermined time of day.

In some embodiments, the at least one predetermined time of day includesat least one default predetermined time of day. In some embodiments, theat least one predetermined time of day includes at least one time of daycoinciding with at least one predetermined mealtime.

In some embodiments, the at least one predetermined time of day includesat least one time of day coinciding with at least one predeterminedmealtime in a time zone of the origin location of the subject.

In some embodiments, the at least one predetermined time of day includesat least one time of day coinciding with at least one predeterminedmealtime in a time zone of the destination location of the subject.

In some embodiments, the at least one predetermined mealtime includes atleast one default mealtime.

In some embodiments, the at least one default mealtime includes adefault breakfast time. In some embodiments, the default breakfast timeis between 5 am and 10 am, between 6 am and 10 am, between 6 am and 9am, between 6 am and 8 am, between 7 am and 10 am, between 7 am and 9am, and between 7 am and 8 am.

In some embodiments, the at least one default mealtime includes adefault lunchtime. In some embodiments, the default lunchtime is between12 pm and 3 pm, between 12 pm and 2 pm, or between 1 pm and 3 pm.

In some embodiments, the at least one default mealtime includes adefault suppertime. In some embodiments, the default suppertime isbetween 6 pm and 10 pm, between 7 pm and 10 pm, between Bpm and 10 pm,between 6 pm and 9 pm, between 7 pm and 9 pm, or between 6 pm and 8 pm.

In some embodiments, the at least one predetermined time of day includesat least two predetermined times of day. In some embodiments, the atleast two predetermined times of day include lunchtime. In someembodiments, the at least two predetermined times of day includesuppertime. In some embodiments, the at least two predetermined times ofday include at least two mealtimes. In some embodiments, the at leasttwo mealtimes include lunchtime and suppertime.

In some embodiments, activation of the vibrating agitator to operate inthe first vibrating mode of operation at the at least one predeterminedtime of day triggers a spontaneous bowel movement (SBM) in the user,which SBM occurs at a later time of day than the at least onepredetermined time of day.

In some embodiments, activation of the vibrating agitator to operate inthe first vibrating mode of operation at the at least one predeterminedtime of day triggers a complete spontaneous bowel movement (CSBM) in theuser, which CSBM occurs at a later time of day than the at least onepredetermined time of day. In some such embodiments, the at least onepredetermined time of day is lunchtime, for example between 12 pm to 3pm or between 12 pm to 2 pm, and the later time of day is dinnertime,for example between 6 pm and 9 pm.

In some embodiments, at least one of the capsule and the control unitincludes an input mechanism for receiving subject-specific input fromthe subject, and wherein the at least one predetermined mealtimeincludes at least one subject-specific mealtime of the subject.

In some such embodiments, the subject-specific mealtime of the subjectis a subject-specific mealtime in the time zone of the origin locationof the subject. In other such embodiments, the subject-specific mealtimeof the subject is a subject-specific mealtime in the time zone of thedestination location of the subject.

In some embodiments, at least one of the capsule and the control unitincludes a location sensor adapted to identify a geographical region inwhich the capsule is located, and wherein the at least one predeterminedtime of day includes at least one region-specific time of day of thegeographical region in which the capsule is located. In some suchembodiments, the at least one region-specific time of day includes atleast one region-specific mealtime of the geographical region in whichthe capsule is located.

In some such embodiments, the geographical region is a geographicalregion of the origin location of the subject. In other such embodiments,the geographical region is a geographical region of the destinationlocation of the subject.

In some embodiments, the activation input additionally includes avibration protocol to be used by the vibrating agitator during the firstvibrating mode of operation.

In some embodiments, the controller is adapted to activate the agitationvibration mechanism to operate in the first vibrating mode of operationat the at least one predetermined time of day only if a minimum delayduration has passed between receipt of the activation input and the atleast one predetermined time of day.

In some embodiments, the vibrating agitator includes at least a radialagitator adapted, in the first vibrating mode of operation, to exertradial forces on the housing, in a radial direction with respect to thelongitudinal axis of the housing, thereby to cause the vibrationsexerted by the housing. In some embodiments, the radial agitatorincludes an unbalanced weight attached to a shaft of an electric motorpowered by the power supply.

In some embodiments, the vibrating agitator includes at least an axialagitator adapted, in the first vibrating mode of operation, to exertaxial forces on the housing, in an axial direction with respect to thelongitudinal axis of the housing, thereby to cause the vibrationsexerted by the housing. In some embodiments, the axial agitator includesan electric motor powered by the power supply and an urging mechanism,associated with, and driven by, the electric motor, the urging mechanismadapted to exert the axial forces. In some embodiments, the urgingmechanism is adapted to exert the axial forces in opposite directions.In some embodiments, the urging mechanism is adapted to deliver at leasta portion of the axial forces in a knocking mode.

In some embodiments, the vibrating agitator is adapted in the firstvibrating mode of operation, to exert radial forces on the housing in aradial direction with respect to the longitudinal axis of the housingand to exert axial forces on the housing in an axial direction withrespect to the longitudinal axis of the housing, thereby to cause thevibrations exerted by the housing. In some embodiments, the vibratingagitator includes a radial agitator adapted to exert the radial forcesand a separate axial agitator adapted to exert the axial forces. Inother embodiments, the vibrating agitator includes a single agitatoradapted to exert the radial forces and the axial forces.

In some embodiments, the housing includes first and second members, andthe vibrating agitator includes a mechanism adapted to effect vibrationsby moving the first member of the housing in the opposite directionrelative to the second member of the housing.

In some embodiments, the vibrating mode of operation including aplurality of cycles, each of the cycles including a vibration durationfollowed by a repose duration, wherein the housing exerts the vibrationsduring the vibration duration. In some embodiments, the repose durationis greater than the vibration duration.

In some embodiments, the vibration duration is in the range of 0.1second to 10 seconds, 1 second to 10 seconds, 1 second to 9 seconds, 2seconds to 9 seconds, 3 seconds to 9 seconds, 3 seconds to 8 seconds, 3seconds to 7 seconds, 3 seconds to 6 seconds, 4 seconds to 6 seconds, or5 seconds to 6 seconds.

In some embodiments, the repose duration is in the range of 1 second to180 seconds, 3 seconds to 180 seconds, 5 seconds to 180 seconds, 5seconds to 150 seconds, 5 seconds to 120 seconds, 8 seconds to 100seconds, 8 seconds to 30 seconds, 10 seconds to 80 seconds, 10 secondsto 70 seconds, 10 seconds to 60 seconds, 10 seconds to 50 seconds, 10seconds to 40 seconds, 10 seconds to 30 seconds, 10 seconds to 20seconds, or 15 seconds to 20 seconds.

In some embodiments, a duration of each of the plurality of cycles is inthe range of 1.1 seconds to 200 seconds, 5 seconds to 200 seconds, 10seconds to 200 seconds, 10 seconds to 150 seconds, 10 seconds to 100seconds, 10 seconds to 80 seconds, 10 seconds to 50 seconds, 10 secondsto 40 seconds, 10 seconds to 30 seconds, 15 seconds to 50 seconds, 15seconds to 40 seconds, 15 seconds to 30 seconds, or 15 seconds to 25seconds.

In some embodiments, a cumulative duration of the vibrating mode ofoperation is in the range of 1 hour to 12 hours, 2 hours to 10 hours, 2hours to 8 hours, 2 hours to 6 hours, 2 hours to 4 hours, or 2 hours to3 hours. In some embodiments, the cumulative duration is dependent onproperties of the battery.

In some embodiments, the vibrating agitator is configured such that anet force exerted by the housing on the environment is in the range of50 grams-force to 600 grams-force.

In some embodiments, the vibrating agitator is configured to exert theforces on the housing to attain a vibrational frequency within a rangeof 10 Hz to 650 Hz, 15 Hz to 600 Hz, 20 Hz to 550 Hz, 30 Hz to 550 Hz,50 Hz to 500 Hz, 70 Hz to 500 Hz, 100 Hz to 500 Hz, 130 Hz to 500 Hz, or150 Hz to 500 Hz.

In some embodiments, the controlling of the vibrating agitator iseffected so as to effect a mechanical stimulation of the wall of thegastrointestinal tract during the at least one predetermined time ofday.

In accordance with another embodiment of the present invention there isprovided a gastrointestinal capsule adapted to treat a gastrointestinaltract of a subject following ingestion of the gastrointestinal capsule,the gastrointestinal capsule including:

(a) a housing;

(b) a vibrating agitator adapted such that, in a first vibrating mode ofoperation, the housing exerts vibrations on an environment surroundingthe capsule;

(c) a power supply disposed within the housing and adapted to power thevibrating agitator;

(d) at least one sensor adapted to identify ingestion of thegastrointestinal capsule;

(e) a clock; and

(f) a controller adapted preset with at least one predetermined time ofday and functionally associated with the at least one sensor and withthe clock, the controller adapted, in response to receipt of input fromthe at least one sensor indication ingestion of the gastrointestinalcapsule, using the clock, to track time to occurrence of the at leastone predetermined time of day and to activate the vibrating agitator tooperate in the first vibrating mode of operation at the at least onepredetermined time of day.

In some embodiments, the at least one predetermined time of day is adefault time of day. In some embodiments the at least one predeterminedtime of day is a default mealtime.

In some embodiments, the at least one predetermined time of day includesat least two predetermined times of day. In some embodiments, the atleast two predetermined times of day include lunchtime. In someembodiments, the at least two predetermined times of day includesuppertime. In some embodiments, the at least two predetermined times ofday include at least two mealtimes. In some embodiments, the at leasttwo mealtimes include lunchtime and suppertime.

In some embodiments the clock is set to a default time zone. In someembodiments, the at least one predetermined time of day is set accordingto a typical circadian cycle of subjects in the default time zone.

In some embodiments the gastrointestinal capsule further includes alocation sensor functionally associated with the controller, and thecontroller is further adapted, upon receipt of an input from thelocation sensor indicating a change in location, to activate thevibrating agitator to operate in the first vibrating mode of operationat the at least one predetermined time of day in accordance with adestination time zone.

In accordance with yet another embodiment of the present invention thereis provided a system for treating a gastrointestinal tract of a subject,the system including:

a gastrointestinal capsule including:

-   -   (a) a housing;    -   (b) a vibrating agitator adapted such that, in a first vibrating        mode of operation, the housing exerts vibrations on an        environment surrounding the capsule;    -   (c) a power supply disposed within the housing and adapted to        power the vibrating agitator;    -   (d) a clock;    -   (e) a first communication interface, such as a transceiver; and    -   (f) a controller preset with at least one predetermined time of        day and functionally associated with the clock and with the        communication interface, the controller adapted, in response to        receipt of an activation input, using the clock, to track time        to occurrence of the at least one predetermined time of day and        to activate the vibrating agitator to operate in the first        vibrating mode of operation at the at least one predetermined        time of day; and

a control unit including a second communication interface, said controlunit adapted to provide the activation input to the capsule.

In some embodiments, the control unit is adapted to provide theactivation input prior to the subject ingesting the gastrointestinalcapsule.

In some embodiments, the control unit further includes a sensor adaptedto sense the presence of the gastrointestinal capsule in or on thecontrol unit, and the control unit is adapted to provide the activationinput in response to receipt of an input from the sensor indicating thatthe gastrointestinal capsule is in or on the control unit, for at leasta predetermined duration.

In some embodiments, the control unit further includes a user interface,and is adapted to provide the activation input in response to receipt ofa user input, via the user interface, the user input indicating that thesubject will soon ingest the capsule.

In some embodiments, the control unit is devoid of a timing mechanism.

In some embodiments, the at least one predetermined time of day is adefault time of day. In some embodiments the at least one predeterminedtime of day is a default mealtime.

In some embodiments, the at least one predetermined time of day includesat least two predetermined times of day. In some embodiments, the atleast two predetermined times of day include lunchtime. In someembodiments, the at least two predetermined times of day includesuppertime. In some embodiments, the at least two predetermined times ofday include at least two mealtimes. In some embodiments, the at leasttwo mealtimes include lunchtime and suppertime.

In some embodiments the clock is set to a default time zone. In someembodiments, the at least one predetermined time of day is set accordingto a typical circadian cycle of subjects in the default time zone.

In some embodiments the gastrointestinal capsule further includes alocation sensor functionally associated with the controller, and thecontroller is further adapted, upon receipt of an input from thelocation sensor indicating a change in location, to activate thevibrating agitator to operate in the first vibrating mode of operationat the at least one predetermined time of day in accordance with adestination time zone.

In accordance with a further embodiment of the present invention thereis provided a system for treating a gastrointestinal tract of a subject,the system including:

a gastrointestinal capsule including:

-   -   (a) a housing;    -   (b) a vibrating agitator adapted such that, in a first vibrating        mode of operation, the housing exerts vibrations on an        environment surrounding the capsule;    -   (c) a power supply disposed within the housing and adapted to        power the vibrating agitator;    -   (d) a clock;    -   (e) a first communication interface, such as a transceiver; and    -   (f) a controller functionally associated with the clock and with        the communication interface, the controller adapted, in response        to receipt of an activation input including at least one        predetermined time of day, using the clock, to track time to        occurrence of the at least one predetermined time of day and to        activate the vibrating agitator to operate in the first        vibrating mode of operation at the at least one predetermined        time of day; and

a control unit including a second communication interface, said controlunit adapted to provide the activation input including the at least onepredetermined time of day to the capsule.

In some embodiments, the control unit is adapted to provide theactivation input prior to the subject ingesting the gastrointestinalcapsule.

In some embodiments, the control unit further includes a sensor adaptedto sense the presence of the gastrointestinal capsule in or on thecontrol unit, and the control unit is adapted to provide the activationinput in response to receipt of an input from the sensor indicating thatthe gastrointestinal capsule is in or on the control unit, for at leasta predetermined duration.

In some embodiments, the control unit further includes a user interface,and is adapted to provide the activation input in response to receipt ofa user input, via the user interface, the user input indicating that thesubject will soon ingest the capsule.

In some embodiments, the control unit is devoid of a timing mechanism.

In some embodiments, the at least one time of day is preset in thecontrol unit. In some embodiments, the at least one predetermined timeof day is a default time of day. In some embodiments the at least onepredetermined time of day is a default mealtime.

In some embodiments, the at least one predetermined time of day includesat least two predetermined times of day. In some embodiments, the atleast two predetermined times of day include lunchtime. In someembodiments, the at least two predetermined times of day includesuppertime. In some embodiments, the at least two predetermined times ofday include at least two mealtimes. In some embodiments, the at leasttwo mealtimes include lunchtime and suppertime.

In some embodiments, the control unit is further adapted to compute theat least one time of day.

In some such embodiments, the control unit further includes a userinterface, and is adapted to compute the at least one time of day basedon a user input received via the user interface. In some embodiments theuser input includes at least one of a sleep schedule and a meal scheduleof the subject.

In some embodiments, the control unit further includes a locationsensor, and is adapted to compute the at least one time of day based ona location of the control unit.

In some embodiments the gastrointestinal capsule further includes alocation sensor functionally associated with the controller, and thecontroller is further adapted, upon receipt of an input from thelocation sensor indicating a change in location, to activate thevibrating agitator to operate in the first vibrating mode of operationat the at least one predetermined time of day in accordance with adestination time zone.

In accordance with a further embodiment of the present invention thereis provided a system for treating a gastrointestinal tract of a subject,the system including:

a gastrointestinal capsule including:

-   -   (a) a housing;    -   (b) a vibrating agitator adapted such that, in a first vibrating        mode of operation, the housing exerts vibrations on an        environment surrounding the capsule;    -   (c) a power supply disposed within the housing and adapted to        power the vibrating agitator;    -   (d) a timer;    -   (e) a first communication interface, such as a transceiver; and    -   (f) a controller functionally associated with the timer and with        the communication interface, the controller adapted, in response        to receipt of an activation input including at least one time        delay, using the timer, to track passage of time to completion        of the time delay and to activate the vibrating agitator to        operate in the first vibrating mode of operation; and

a control unit including a clock and a second communication interface,said control unit adapted to:

-   -   compute a time delay from a current time to at least one        predetermined time of day; and    -   provide to the gastrointestinal capsule the activation input        including the computed time delay,

wherein the controller is adapted to activate the vibrating agitator tooperate in the first vibrating mode of operation at the at least onepredetermined time of day.

In some embodiments, the control unit is adapted to provide theactivation input prior to the subject ingesting the gastrointestinalcapsule.

In some embodiments, the control unit further includes a sensor adaptedto sense the presence of the gastrointestinal capsule in or on thecontrol unit, and the control unit is adapted to provide the activationinput in response to receipt of an input from the sensor indicating thatthe gastrointestinal capsule is in or on the control unit, for at leasta predetermined duration.

In some embodiments, the control unit further includes a user interface,and is adapted to provide the activation input in response to receipt ofa user input, via the user interface, the user input indicating that thesubject will soon ingest the capsule.

In some embodiments, the at least one time of day is preset in thecontrol unit. In some embodiments, the at least one predetermined timeof day is a default time of day. In some embodiments the at least onepredetermined time of day is a default mealtime.

In some embodiments, the control unit is further adapted to compute theat least one time of day.

In some such embodiments, the control unit further includes a userinterface, and is adapted to compute the at least one time of day basedon a user input received via the user interface. In some embodiments theuser input includes at least one of a sleep schedule and a meal scheduleof the subject.

In some embodiments, the control unit further includes a locationsensor, and is adapted to compute the at least one time of day based ona location of the control unit.

In accordance with a further embodiment of the present invention thereis provided a system for treating a gastrointestinal tract of a subject,the system including:

a gastrointestinal capsule including:

-   -   (a) a housing;    -   (b) a vibrating agitator adapted such that, in a first vibrating        mode of operation, the housing exerts vibrations on an        environment surrounding the capsule;    -   (c) a power supply disposed within the housing and adapted to        power the vibrating agitator;    -   (d) a first communication interface, such as a transceiver; and    -   (e) a controller functionally associated with the communication        interface, the controller adapted, in response to receipt of an        activation input, to substantially immediately activate the        vibrating agitator to operate in the first vibrating mode of        operation; and

a control unit including a clock and a second communication interface,said control unit adapted to provide to the gastrointestinal capsule theactivation input at at least one predetermined time of day, followingingestion of the gastrointestinal capsule.

In some embodiments, the at least one time of day is preset in thecontrol unit. In some embodiments, the at least one predetermined timeof day is a default time of day. In some embodiments the at least onepredetermined time of day is a default mealtime.

In some embodiments, the at least one predetermined time of day includesat least two predetermined times of day. In some embodiments, the atleast two predetermined times of day include lunchtime. In someembodiments, the at least two predetermined times of day includesuppertime. In some embodiments, the at least two predetermined times ofday include at least two mealtimes. In some embodiments, the at leasttwo mealtimes include lunchtime and suppertime.

In some embodiments, the control unit is further adapted to compute theat least one time of day.

In some such embodiments, the control unit further includes a userinterface, and is adapted to compute the at least one time of day basedon a user input received via the user interface. In some embodiments theuser input includes at least one of a sleep schedule and a meal scheduleof the subject.

In some embodiments, the control unit further includes a locationsensor, and is adapted to compute the at least one time of day based ona location of the control unit.

In some embodiments, the gastrointestinal capsule is devoid of a timingmechanism.

In accordance with a further embodiment of the present invention thereis provided a method of treating the gastrointestinal tract of asubject, the method including:

(a) providing the gastrointestinal capsule as described herein;(b) ingesting the gastrointestinal capsule; and(c) controlling the vibrating agitator such that the first vibratingmode of operation occurs at the at least one predetermined time of day.

In accordance with another embodiment of the present invention there isprovided a method of treating the gastrointestinal tract of a subject,the method including:

(a) providing a gastrointestinal capsule, adapted to transit agastrointestinal tract of the subject, the capsule having:

-   -   (1) a housing arranged along a longitudinal axis;    -   (2) a vibrating agitator, adapted such that, in a first        vibrating mode of operation, the housing exerts vibrations on an        environment surrounding the capsule;    -   (3) a power supply disposed within the housing and adapted to        power the vibrating agitator; and    -   (4) a controller adapted, to activate the vibrating agitator to        operate in the first vibrating mode of operation;        (b) receiving at least one capsule activation input;        (c) ingesting the gastrointestinal capsule; and        (d) responsive to the capsule activation input, controlling the        vibrating agitator such that the first vibrating mode of        operation occurs at the at least one predetermined time of day.

In accordance with yet another embodiment of the present invention thereis provided a method of treating the gastrointestinal tract of asubject, the method including:

(a) providing a gastrointestinal capsule, adapted to transit agastrointestinal tract of the subject, the capsule having:

-   -   (1) a housing arranged along a longitudinal axis;    -   (2) a vibrating agitator, adapted such that, in a first        vibrating mode of operation, the housing exerts vibrations on an        environment surrounding the capsule;    -   (3) a power supply disposed within the housing and adapted to        power the vibrating agitator; and    -   (4) a controller adapted, to activate the vibrating agitator to        operate in the first vibrating mode of operation;        (b) ingesting the gastrointestinal capsule; and        (c) when the gastrointestinal capsule is in an operative state,        controlling the vibrating agitator such that the first vibrating        mode of operation occurs at the at least one predetermined time        of day.

In some embodiments, the method is adapted for treating an ailment ofthe gastrointestinal tract of the subject.

In some embodiments, the subject is travelling from an origin locationto a destination location, and the method is adapted for mitigatingjetlag of the subject.

In some such embodiments, the first vibrating mode of operation occursat the at least one predetermined time of day according to the time zoneof the origin location.

In other such embodiments, the first vibrating mode of operation occursat the at least one predetermined time of day according to the time zoneof the destination location.

In yet other such embodiments, the first vibrating mode of operationoccurs, at a first time of day of the at least one predetermined time ofday according to the time zone of the origin location, and at a secondtime of day of the at least one predetermined time of day according tothe time zone of the destination location.

In some embodiments, the predetermined time of day is selected accordingto a circadian cycle of the subject.

In some embodiments, the predetermined time of day is selected accordingto a gastric pH profile of the subject.

In some embodiments, providing a gastrointestinal capsule includesproviding the gastrointestinal capsule in an inoperative state, themethod further including, at the capsule, receiving an activation inputtransitioning the capsule from the inoperative state to the operativestate.

In some embodiments, providing the gastrointestinal capsule includesproviding the gastrointestinal capsule including at least one timingmechanism, and devoid of sensors for sensing an environment thereof. Insome such embodiments the at least one timing mechanism comprises aclock. In other embodiments the at least one timing mechanism comprisesa timer.

In some embodiments, the controlling includes, responsive to theactivation input, waiting a predetermined delay time, and following thepredetermined delay time, at a time coinciding with the at least onepredetermined time of day, activating the vibrating agitator to operatein the first vibration mode of operation.

In some embodiments, receiving the at least one activation inputincludes receiving the at least one activation input from at least onesensor forming part of the gastrointestinal capsule.

In some embodiments, the at least one sensor includes an illuminationsensor, and the receiving the at least one activation input includesreceiving input indicating transition of the capsule from an illuminatedenvironment to a dark environment.

In some embodiments, the at least one sensor includes a pressure sensor,and the receiving the at least one activation input includes receivinginput indicating pressure applied to the capsule, which pressure isindicative of the capsule moving through a pharynx of the subject.

In some embodiments, the at least one sensor includes a temperaturesensor, and the receiving the at least one activation input includesreceiving input indicating transition of the capsule from an area withambient temperature to an area with a human body temperature.

In some embodiments, the at least one sensor includes an accelerometer,and the receiving the at least one activation input includes receivingthe activation input in response to a detected activation motion carriedout with the gastrointestinal capsule.

In some embodiments, the at least one sensor includes a moisture sensor,and the receiving the at least one activation input includes receivinginput indicating transition of the capsule from a dry environment to ahumid environment.

In some embodiments, the capsule further including a timing mechanism,the method further including, in response to the receiving theactivation input, activating operation of the timing mechanism to tracka time of day so as to identify the at least one predetermined time ofday for activation of the vibration agitator.

In some embodiments, receiving the activation input includes receivingthe activation input from a control unit remote from thegastrointestinal capsule.

In some embodiments, receiving the activation input includes receivingthe activation input following the ingesting. In other embodiments,receiving the activation input includes receiving the activation inputprior to the ingesting.

In some embodiments, receiving the activation input includes receiving acurrent time of day, and the controlling the vibration agitator includescomputing a delay time from the current time of day to the at least onepredetermined time of day and activating the vibrating agitator tooperate in the first vibration mode of operation following the delaytime.

In some embodiments, the activation input indicates that a current timeof day is the at least one predetermined time of day, and controllingthe vibration agitator to operate in the first vibration mode ofoperation occurs immediately following the receiving of the activationinput.

In some embodiments, receiving the activation input includes receivingan indication of a delay time from the current time to the at least onepredetermined time of day and activating the vibrating agitator tooperate in the first vibration mode of operation following the delaytime. In some such embodiments the timing mechanism of the capsulecomprises a timer.

In some embodiments, the current time of day is the current time of dayin the origin location of the subject. In other embodiments, the currenttime of day is the current time of day in the destination location ofthe subject.

In some embodiments, the activation input includes the at least onepredetermined time of day.

In some embodiments, the at least one predetermined time of day includesat least one default predetermined time of day. In some embodiments, theat least one predetermined time of day includes at least one time of daycoinciding with at least one predetermined mealtime.

In some embodiments, the at least one predetermined mealtime is apredetermined mealtime in the time zone of the origin location of thesubject. In other embodiments, the at least one predetermined mealtimeis a predetermined mealtime in the time zone of the destination locationof the subject.

In some embodiments, the at least one predetermined mealtime includes atleast one default mealtime.

In some embodiments, the at least one default mealtime includes adefault breakfast time. In some embodiments, the default breakfast timeis between 5 am and 10 am, between 6 am and 10 am, between 6 am and 9am, between 6 am and 8 am, between 7 am and 10 am, between 7 am and 9am, and between 7 am and 8 am.

In some embodiments, the at least one default mealtime includes adefault lunchtime. In some embodiments, the default lunchtime is between12 pm and 3 pm, between 12 pm and 2 pm, or between 1 pm and 3 pm.

In some embodiments, the at least one default mealtime includes adefault suppertime. In some embodiments, the default suppertime isbetween 6 pm and 10 pm, between 7 pm and 10 pm, between Bpm and 10 pm,between 6 pm and 9 pm, between 7 pm and 9 pm, or between 6 pm and 8 pm.

In some embodiments, the at least one predetermined time of day includesat least two predetermined times of day. In some embodiments, the atleast two predetermined times of day include lunchtime. In someembodiments, the at least two predetermined times of day includesuppertime. In some embodiments, the at least two predetermined times ofday include at least two mealtimes. In some embodiments, the at leasttwo mealtimes include lunchtime and suppertime.

In some embodiments, activation of the vibrating agitator to operate inthe first vibrating mode of operation at the at least one predeterminedtime of day triggers a spontaneous bowel movement (SBM) in the user,which SBM occurs at a later time of day than the at least onepredetermined time of day.

In some embodiments, activation of the vibrating agitator to operate inthe first vibrating mode of operation at the at least one predeterminedtime of day triggers a complete spontaneous bowel movement (CSBM) in theuser, which CSBM occurs at a later time of day than the at least onepredetermined time of day.

In some such embodiments, the at least one predetermined time of day islunchtime, for example between 12 pm to 3 pm or between 12 pm to 2 pm,and the later time of day is dinnertime, for example between 6 pm and 9pm.

In some embodiments, the method further includes, prior to thecontrolling, receiving subject-specific input relating to at least onesubject-specific mealtime of the subject, and wherein the at least onepredetermined mealtime includes the at least one subject-specificmealtime.

In some embodiments, the at least one subject-specific mealtime is asubject-specific mealtime in the time zone of the origin location of thesubject. In other embodiments, the at least subject-specific mealtime isa subject-specific mealtime in the time zone of the destination locationof the subject.

In some embodiments, the method further includes, prior to thecontrolling, receiving regional information relating to a geographicalregion in which the gastrointestinal capsule is located, and wherein theat least one predetermined time of day includes at least oneregion-specific time of day of the geographical region. In someembodiments, the at least one region-specific time of day comprises aregion-specific mealtime of the geographical region.

In some embodiments, the geographical region is a geographical region ofthe origin location of the subject. In other embodiments, thegeographical region is a geographical region of the destination locationof the subject.

In some embodiments, receiving the regional information includesreceiving an identification of the geographical region. In someembodiments, the identification of the geographical region is receivedfrom a location sensor. In some embodiments, receiving the regionalinformation includes receiving the at least one region-specific time ofday of the geographical region. In some embodiments, receiving theregional information includes receiving the at least one region-specificmealtime of the geographical region.

In some embodiments, receiving regional information occurs in a controlunit remote from the gastrointestinal capsule prior to thegastrointestinal capsule receiving the activation input, and wherein thereceiving the activation input includes receiving activation input beingon the received regional information.

In some embodiments, receiving regional information is carried out bythe controller of the gastrointestinal capsule.

In some embodiments, receiving the activation input additionallyincludes receiving a vibration protocol to be used by the controller tocontrol operation of the vibrating agitator.

In some embodiments, the vibrating agitator includes at least a radialagitator, and the controlling includes controlling the radial agitator,in the first vibrating mode of operation, to exert radial forces on thehousing, in a radial direction with respect to the longitudinal axis ofthe housing, thereby to cause the vibrations exerted by the housing.

In some embodiments, the vibrating agitator includes at least an axialagitator, and the controlling includes controlling the axial agitator,in the first vibrating mode of operation, to exert axial forces on thehousing, in an axial direction with respect to the longitudinal axis ofthe housing, thereby to cause the vibrations exerted by the housing.

In some embodiments, the controlling includes controlling the vibratingagitator, in the first vibrating mode of operation, to exert radialforces on the housing in a radial direction with respect to thelongitudinal axis of the housing and to exert axial forces on thehousing in an axial direction with respect to the longitudinal axis ofthe housing, thereby to cause the vibrations exerted by the housing.

In some embodiments, the vibrating agitator includes a radial agitatoradapted to exert the radial forces and a separate axial agitator adaptedto exert the axial forces.

In some embodiments, the vibrating agitator includes a single agitatoradapted to exert the radial forces and the axial forces.

In some embodiments, the housing includes first and second members, andcontrolling the vibrating agitator includes effecting a vibration bymoving the first member of the housing in the opposite directionrelative to the second member of the housing.

In some embodiments, controlling the vibrating agitator includescontrolling the vibrating mode of operation to include a plurality ofcycles, each of the cycles including a vibration duration followed by arepose duration, wherein the housing exerts the vibrations during thevibration duration.

In some embodiments, the repose duration is greater than the vibrationduration.

In some embodiments, the vibration duration is in the range of 0.1second to 10 seconds, 1 second to 10 seconds, 1 second to 9 seconds, 2seconds to 9 seconds, 3 seconds to 9 seconds, 3 seconds to 8 seconds, 3seconds to 7 seconds, 3 seconds to 6 seconds, 4 seconds to 6 seconds, or5 seconds to 6 seconds.

In some embodiments, the repose duration is in the range of 1 second to180 seconds, 3 seconds to 180 seconds, 5 seconds to 180 seconds, 5seconds to 150 seconds, 5 seconds to 120 seconds, 8 seconds to 100seconds, 8 seconds to 30 seconds, 10 seconds to 80 seconds, 10 secondsto 70 seconds, 10 seconds to 60 seconds, 10 seconds to 50 seconds, 10seconds to 40 seconds, 10 seconds to 30 seconds, 10 seconds to 20seconds, or 15 seconds to 20 seconds.

In some embodiments, a duration of each of the plurality of cycles is inthe range of 1.1 seconds to 200 seconds, 5 seconds to 200 seconds, 10seconds to 200 seconds, 10 seconds to 150 seconds, 10 seconds to 100seconds, 10 seconds to 80 seconds, 10 seconds to 50 seconds, 10 secondsto 40 seconds, 10 seconds to 30 seconds, 15 seconds to 50 seconds, 15seconds to 40 seconds, 15 seconds to 30 seconds, or 15 seconds to 25seconds.

In some embodiments, controlling the vibrating agitator includescontrolling the vibrating agitator such that a cumulative duration ofthe vibrating mode of operation is in the range of 1 hour to 12 hours, 2hours to 10 hours, 2 hours to 8 hours, 2 hours to 6 hours, 2 hours to 4hours, or 2 hours to 3 hours. In some embodiments, the cumulativeduration is dependent on properties of the battery.

In some embodiments, in the first vibration mode of operation, thevibrating agitator is configured such that a net force exerted by thehousing on the environment is in the range of 50 grams-force to 600grams-force.

In some embodiments, in the first vibration mode of operation thevibrating agitator is configured to exert the forces on the housing toattain a vibrational frequency within a range of 10 Hz to 650 Hz, 15 Hzto 600 Hz, 20 Hz to 550 Hz, 30 Hz to 550 Hz, 50 Hz to 500 Hz, 70 Hz to500 Hz, 100 Hz to 500 Hz, 130 Hz to 500 Hz, or 150 Hz to 500 Hz.

In some embodiments, controlling of the vibrating agitator includescontrolling the vibrating agitator so as to effect a mechanicalstimulation of the wall of the gastrointestinal tract during the atleast one predetermined time of day.

In accordance with another embodiment of the present invention, there isprovided a method of treating the gastrointestinal tract of a subject,the method including ingesting, by the subject, a gastrointestinalcapsule including:

-   -   a housing;    -   a vibrating agitator adapted such that, in a first vibrating        mode of operation, the housing exerts vibrations on an        environment surrounding the gastrointestinal capsule;    -   a power supply disposed within the housing, and adapted to power        the vibrating agitator;    -   at least one sensor adapted to identify ingestion of the        gastrointestinal capsule;    -   a clock; and    -   a controller preset with at least one predetermined time of day        and functionally associated with the at least one sensor and        with the clock, the controller adapted, in response to receipt        of input from the at least one sensor indicating ingestion of        the gastrointestinal capsule, to activate the vibrating agitator        to operate in the first vibrating mode of operation at the at        least one predetermined time of day.

In accordance with yet another embodiment of the present invention,there is provided a method of treating the gastrointestinal tract of asubject, the method including:

providing to the subject, or the subject obtaining, a gastrointestinalcapsule including:

-   -   (a) a housing;    -   (b) a vibrating agitator adapted such that, in a first vibrating        mode of operation, the housing exerts vibrations on an        environment surrounding the capsule;    -   (c) a power supply disposed within the housing and adapted to        power the vibrating agitator;    -   (d) a clock;    -   (e) a first communication interface, such as a transceiver; and    -   (f) a controller preset with at least one predetermined time of        day and functionally associated with the clock and with the        communication interface, the controller adapted, in response to        receipt of an activation input, using the clock, to track time        to occurrence of the at least one predetermined time of day and        to activate the vibrating agitator to operate in the first        vibrating mode of operation at the at least one predetermined        time of day;

triggering, by the subject, a control unit to provide the activationinput to the controller; and

ingesting, by the subject, of the gastrointestinal capsule,

such that the controller activates the vibrating agitator to operate inthe first vibrating mode of operation at the at least one predeterminedtime of day following receipt of the activation input.

In some embodiments, the triggering comprises placing thegastrointestinal capsule in or on the control unit for at least apredetermined duration.

In some embodiments, the triggering comprises providing a user input, tothe control unit, via a user interface. In some such embodiments theuser input is indicative of the subject being ready to ingest thecapsule.

In accordance with a further embodiment of the present invention, thereis provided a method of treating the gastrointestinal tract of asubject, the method including:

providing to the subject, or the subject obtaining, a gastrointestinalcapsule including:

-   -   (a) a housing;    -   (b) a vibrating agitator adapted such that, in a first vibrating        mode of operation, the housing exerts vibrations on an        environment surrounding the capsule;    -   (c) a power supply disposed within the housing and adapted to        power the vibrating agitator;    -   (d) a clock;    -   (e) a first communication interface, such as a transceiver; and    -   (f) a controller functionally associated with the clock and with        the communication interface, the controller adapted, in response        to receipt of an activation input including at least one        predetermined time of day, using the clock, to track time to        occurrence of the at least one predetermined time of day and to        activate the vibrating agitator to operate in the first        vibrating mode of operation at the at least one predetermined        time of day;

triggering, by the subject, a control unit to provide the activationinput including the at least one predetermined time of day to thecontroller; and

ingesting, by the subject, of the gastrointestinal capsule,

such that the controller activates the vibrating agitator to operate inthe first vibrating mode of operation at the at least one predeterminedtime of day following receipt of the activation input.

In some embodiments, the triggering comprises placing thegastrointestinal capsule in or on the control unit for at least apredetermined duration.

In some embodiments, the triggering comprises providing a user input, tothe control unit, via a user interface. In some such embodiments theuser input is indicative of the subject being ready to ingest thecapsule.

In some embodiments, the activation input further includes a vibrationprotocol, such that the controller activates the vibrating agitator tooperate in the first vibrating mode of operation in accordance with thevibrating protocol.

In some embodiments, the at least one time of day is preset in thecontrol unit. In some such embodiments the at least one time of day is adefault time of day.

In some embodiments, the at least one time of day is provided to thecontrol unit as part of a treatment protocol.

In some embodiments, the method further includes, at the control unit,computing the at least one predetermined time of day, prior to providingthe activation input.

In some embodiments, the method further includes, at the control unit,receiving user input, and computing the at least one predetermined timeof day based on the received user input.

In accordance with another embodiment of the present invention, there isprovided a method of treating the gastrointestinal tract of a subject,the method including:

providing to the subject, or the subject obtaining, a gastrointestinalcapsule including:

-   -   (a) a housing;    -   (b) a vibrating agitator adapted such that, in a first vibrating        mode of operation, the housing exerts vibrations on an        environment surrounding the capsule;    -   (c) a power supply disposed within the housing and adapted to        power the vibrating agitator;    -   (d) a timer;    -   (e) a first communication interface, such as a transceiver; and    -   (f) a controller functionally associated with the timer and with        the communication interface, the controller adapted, in response        to receipt of an activation input providing at least one time        delay, using the timer, to track passage of time to completion        of the at least one time delay and to activate the vibrating        agitator to operate in the first vibrating mode of operation;

triggering, by the subject, a control unit to provide the activationinput including the at least one time delay to the controller; and

ingesting, by the subject, of the gastrointestinal capsule,

such that the controller activates the vibrating agitator to operate inthe first vibrating mode of operation following the at least one timedelay, at a time coincidental with at least one predetermined time ofday.

In some embodiments, the triggering comprises placing thegastrointestinal capsule in or on the control unit for at least apredetermined duration.

In some embodiments, the triggering comprises providing a user input, tothe control unit, via a user interface. In some such embodiments theuser input is indicative of the subject being ready to ingest thecapsule.

In some embodiments, the activation input further includes a vibrationprotocol, such that the controller activates the vibrating agitator tooperate in the first vibrating mode of operation in accordance with thevibrating protocol.

In some embodiments, the method further includes, at the control unit,computing the at least one time delay from the current time to the atleast one predetermined time of day.

In some embodiments, the at least one time of day is preset in thecontrol unit. In some such embodiments the at least one time of day is adefault time of day.

In some embodiments, the at least one time of day is provided to thecontrol unit as part of a treatment protocol.

In some embodiments, the method further includes, at the control unit,computing the at least one predetermined time of day, prior to providingthe activation input.

In some embodiments, the method further includes, at the control unit,receiving user input, and computing the at least one predetermined timeof day based on the received user input.

In accordance with yet another embodiment of the present invention thereis provided a method of treating the gastrointestinal tract of asubject, the method including:

providing to the subject, or the subject obtaining, a gastrointestinalcapsule including:

-   -   (a) a housing;    -   (b) a vibrating agitator adapted such that, in a first vibrating        mode of operation, the housing exerts vibrations on an        environment surrounding the capsule;    -   (c) a power supply disposed within the housing and adapted to        power the vibrating agitator;    -   (d) a first communication interface, such as a transceiver; and    -   (e) a controller functionally associated with the communication        interface, the controller adapted, in response to receipt of an        activation input, to substantially immediately activate the        vibrating agitator to operate in the first vibrating mode of        operation;

ingesting, by the subject, of the gastrointestinal capsule,

following the ingesting, at at least one predetermined time of day,automatically providing an activation input from a control unit to thegastrointestinal capsule, thereby causing the controller to controlvibrating agitator to operate in the first vibrating mode of operationat the at least one predetermined time of day.

In some embodiments, the activation input further includes a vibrationprotocol, such that the controller activates the vibrating agitator tooperate in the first vibrating mode of operation in accordance with thevibrating protocol.

In some embodiments, the at least one time of day is preset in thecontrol unit. In some such embodiments the at least one time of day is adefault time of day.

In some embodiments, the at least one time of day is provided to thecontrol unit as part of a treatment protocol.

In some embodiments, the method further includes, at the control unit,computing the at least one predetermined time of day, prior to providingthe activation input.

In some embodiments, the method further includes, at the control unit,receiving user input, and computing the at least one predetermined timeof day based on the received user input.

There is further provided in accordance with an embodiment of thepresent invention a gastrointestinal treatment system including agastrointestinal capsule for vibrating in a gastrointestinal tract of asubject following ingestion of the gastrointestinal capsule, thegastrointestinal capsule including:

(a) a housing having a longitudinal axis;(b) a vibrating agitator adapted such that, in a first vibrating mode ofoperation, the housing exerts vibrations on an environment surroundingthe capsule;(c) a power supply disposed within the housing and adapted to power thevibrating agitator; and(d) a controller adapted, in response to receipt of an activation input,to activate the vibrating agitator to operate in the first vibratingmode of operation at at least two predetermined times of day.

In some embodiments, the at least two predetermined times of day areselected according to a circadian cycle of the subject.

In some embodiments, one of the at least two predetermined times of dayis a lunchtime. In some embodiments, the lunchtime is a defaultlunchtime. In some embodiments, the lunchtime is a subject-specificlunchtime. In some embodiments, the lunchtime is a region-specificlunchtime.

In some embodiments, one of the at least two predetermined times of dayis a suppertime. In some embodiments, the suppertime is a defaultsuppertime. In some embodiments, the suppertime is a subject-specificsuppertime. In some embodiments, the suppertime is a region-specificsuppertime.

There is additionally provided in accordance with an embodiment of thepresent invention a method of treating constipation of a subject, themethod including:

(a) providing to the subject a gastrointestinal capsule for ingestionthereof, the gastrointestinal capsule being adapted to transit agastrointestinal tract of the subject, the gastrointestinal capsulehaving:

-   -   (1) a housing arranged along a longitudinal axis;    -   (2) a vibrating agitator, the vibrating agitation mechanism        adapted such that, in a first vibrating mode of operation, the        housing exerts vibrations on an environment surrounding the        gastrointestinal capsule;    -   (3) a power supply disposed within the housing and adapted to        power the vibrating agitator; and    -   (4) a controller adapted to activate the vibrating agitator to        operate in the first vibrating mode of operation;        (b) following ingestion of the gastrointestinal capsule by the        subject, and when the gastrointestinal capsule is in an        operative state, activating the vibrating agitator to operate in        the first vibrating mode of operation at at least two        predetermined times of day; and        (c) repeating steps (a) and (b), which together form a treatment        session, one to seven times per week, thereby to treat        constipation of the subject.

In some embodiments, the method further includes receiving inputrelating a circadian cycle of the subject, and the at least twopredetermined times of day are selected according to the circadian cycleof the subject.

In some embodiments, one of the at least two predetermined times of dayis a lunchtime. In some embodiments, the lunchtime is a defaultlunchtime. In some embodiments, the lunchtime is a subject-specificlunchtime. In some embodiments, the lunchtime is a region-specificlunchtime.

In some embodiments, one of the at least two predetermined times of dayis a suppertime. In some embodiments, the suppertime is a defaultsuppertime. In some embodiments, the suppertime is a subject-specificsuppertime. In some embodiments, the suppertime is a region-specificsuppertime.

There is also provided in accordance with an embodiment of the presentinvention a method of increasing a number of spontaneous bowel movements(SBMs) or of complete spontaneous bowel movements (CSBMs) that a subjectexperiences per week, the method including:

(a) obtaining a baseline number of SBMs or of CSBMs that the subject hasper week;(b) providing to the subject a gastrointestinal capsule for ingestionthereof, the gastrointestinal capsule being adapted to transit agastrointestinal tract of the subject, the gastrointestinal capsulehaving:

-   -   (1) a housing arranged along a longitudinal axis;    -   (2) a vibrating agitator, the vibrating agitation mechanism        adapted such that, in a first vibrating mode of operation, the        housing exerts vibrations on an environment surrounding the        gastrointestinal capsule;    -   (3) a power supply disposed within the housing and adapted to        power the vibrating agitator; and    -   (4) a controller adapted to activate the vibrating agitator to        operate in the first vibrating mode of operation;        (c) following ingestion of the gastrointestinal capsule by the        subject, and when the gastrointestinal capsule is in an        operative state, activating the vibrating agitator to operate in        the first vibrating mode of operation at at least two        predetermined times of day on at least two consecutive days,        wherein the at least two predetermined times of day include at        least two predetermined mealtimes; and        (d) repeating steps b and c, which together form a treatment        session, one to seven times per week, for a period of at least        two weeks.

In some embodiments, the repeating of steps b and c increases the numberof SBMs or CSBMs experienced by the user, per week, by at least oneadditional SBM or one additional CSBM for at least two of the fourweeks.

In some embodiments, the method further includes receiving inputrelating a circadian cycle of the subject, and the at least twopredetermined times of day are selected according to the circadian cycleof the subject.

In some embodiments, one of the at least two predetermined times of dayis a lunchtime. In some embodiments, the lunchtime is a defaultlunchtime. In some embodiments, the lunchtime is a subject-specificlunchtime. In some embodiments, the lunchtime is a region-specificlunchtime.

In some embodiments, one of the at least two predetermined times of dayis a suppertime. In some embodiments, the suppertime is a defaultsuppertime. In some embodiments, the suppertime is a subject-specificsuppertime. In some embodiments, the suppertime is a region-specificsuppertime.

In some embodiments, the activating of the vibrating agitator includesactivating the vibrating agitator to operate in the first vibrating modeof operation for a predetermined duration at each time of activationthereof.

In some embodiments, the repeating steps b and c five times per week,for a period of at least two weeks, increases the number of SBMs orCSBMs experienced by the user, per week, by at least one additional SBMor one additional CSBM.

In some embodiments, the repeating steps b and c five times per week,for a period of at least two weeks, increases the number of SBMs orCSBMs experienced by the user, per week, by at least two additional SBMsor two additional CSBMs.

In some embodiments, the increasing of the number of SBMs or CSBMsexperienced by the user per week includes improving a clinicaldefinition criteria or clinical diagnosis of the subject.

There is further provided in accordance with an embodiment of thepresent invention a method of treating a gastrointestinal ailment of asubject, the method including:

(a) providing to the subject a gastrointestinal capsule for ingestionthereof, the gastrointestinal capsule being adapted to transit agastrointestinal tract of the subject, the gastrointestinal capsulehaving:

-   -   (1) a housing arranged along a longitudinal axis;    -   (2) a vibrating agitator, the vibrating agitation mechanism        adapted such that, in a first vibrating mode of operation, the        housing exerts vibrations on an environment surrounding the        gastrointestinal capsule;    -   (3) a power supply disposed within the housing and adapted to        power the vibrating agitator; and    -   (4) a controller adapted to activate the vibrating agitator to        operate in the first vibrating mode of operation;        (b) following ingestion of the gastrointestinal capsule by the        subject, and when the gastrointestinal capsule is in an        operative state, activating the vibrating agitator to operate in        the first vibrating mode of operation at at least one        predetermined time of day on at least two consecutive days; and        (c) repeating steps a and b, which together form a treatment        session, one to seven times per week, thereby to treat at least        one gastrointestinal ailment of the subject,

wherein treating of the gastrointestinal ailment includes at least oneof treating or alleviating constipation of the subject, reducingstraining experienced by the subject during defecating, and increasing aBristol stool score of stool of the subject.

In some embodiments, the method further includes receiving inputrelating a circadian cycle of the subject, and the at least onepredetermined time of day is selected according to the circadian cycleof the subject.

In some embodiments, the at least one predetermined times of day is alunchtime. In some embodiments, the lunchtime is a default lunchtime. Insome embodiments, the lunchtime is a subject-specific lunchtime. In someembodiments, the lunchtime is a region-specific lunchtime.

In some embodiments, the at least one predetermined time of day is asuppertime. In some embodiments, the suppertime is a default suppertime.In some embodiments, the suppertime is a subject-specific suppertime. Insome embodiments, the suppertime is a region-specific suppertime.

In some embodiments, the activating of the vibrating agitator includesactivating the vibrating agitator to operate in the first vibrating modeof operation for a predetermined duration at each activation thereof.

In some embodiments, the repeating the steps (a) and (b) one to seventimes per week includes repeating steps (a) and (b) at least twice perweek on consecutive days, such that first and second thegastrointestinal capsules disposed in two different locations within thegastrointestinal tract of the subject simultaneously, and the activatingthe vibrating agitator to operate in the first vibrating mode ofoperation at the at least one predetermined time of day on twoconsecutive days includes activating the vibrating agitators of thefirst and second gastrointestinal capsules to operate in the firstvibrating mode of operation, simultaneously at the two differentlocations, during the at least one predetermined time of day.

In some embodiments, the method further includes prior to (a), obtaininga baseline number of spontaneous bowel movements (SBM) or of completespontaneous bowel movements (CSBM) that the subject has per week.

In some embodiments, the method further includes repeating steps a-d forat least two weeks, thereby to increase a number of SBMs or CSBMs of thesubject by at least one additional SBM or at least one additional CSBMover the baseline number.

In some embodiments, the method further includes repeating steps a-d forat least two weeks, thereby to increase a number of SBMs or CSBMs of thesubject by at least two additional SBMs or at least one additional CSBMsover the baseline number.

BRIEF DESCRIPTION OF THE FIGURES

The foregoing discussion will be understood more readily from thefollowing detailed description of the invention, when taken inconjunction with the accompanying FIGS. 1A-5B), in which:

FIGS. 1A to 1F are schematic block diagram of various embodiments ofgastrointestinal treatment systems including a vibrating ingestiblecapsule according to the present invention;

FIGS. 2A to 2F are schematic flowcharts of embodiments of methods fortreating the gastrointestinal tract according to the present invention,the treatment methods being based on use of the gastrointestinaltreatment systems of FIGS. 1A to 1F, respectively;

FIG. 3 is a schematic illustration of the circadian cycle of a person,including suitable times of day for the implementation of the methods ofFIGS. 2A to 2F;

FIG. 4 is a graphic illustration of the gastric pH of a person,indicating suitable times of day for the implementation of the methodsof FIGS. 2A to 2F;

FIGS. 5A and 5B are graphic representation of results of clinicalexperiments conducted using an ingestible vibrating gastrointestinalcapsule as illustrated in FIG. 1A and using a method as illustrated inFIG. 2A; and

FIGS. 6A, 6B, 6C, and 6D are graphic representation of results ofadditional clinical experiments conducted using an ingestible vibratinggastrointestinal capsule as illustrated in FIG. 1A and using a method asillustrated in FIG. 2A.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

The principles of the inventive gastrointestinal treatment system andmethod of treating the gastrointestinal tract using the inventivegastrointestinal treatment system, may be better understood withreference to the drawings and the accompanying description.

Before explaining at least one embodiment of the invention in detail, itis to be understood that the invention is not limited in its applicationto the details of construction and the arrangement of the components setforth in the following description or illustrated in the drawings. Theinvention is capable of other embodiments or of being practiced orcarried out in various ways. Also, it is to be understood that thephraseology and terminology employed herein is for the purpose ofdescription and should not be regarded as limiting.

For the purposes of this application, the term “subject” relates to ahuman.

For the purposes of this application, the term “vibrating ingestiblecapsule” relates to an ingestible capsule adapted to at leastintermittently vibrate, for a cumulative duration of at least oneminute, in accordance with a vibration protocol of the capsule.

For the purposes of this application, the term “vibrating agitator”refers to any type of structure or mechanism that vibrates or causeselements in its vicinity to vibrate, including a motor driven agitatorsuch as a motor driven rotor including an eccentric weight, a motordrive pendulum, and a motor driven axial agitator.

For the purposes of this application, the term “intermittently activatedvibrating agitator” refers to a vibrating agitator that vibrates orcauses elements in its vicinity to vibrate and is operative at certaintimes, and does not vibrate or cause elements in its vicinity to vibrateat other times, the activation times being selected by a controller orother control unit controlling the vibrating agitator.

For the purposes of this application, the term “controller”, and theequivalent term “control element” refer to a computing circuit orelement for controlling operation of mechanical and/or electricalcomponents of the capsule, which form part of the capsule. Thecontroller includes a processor or processing unit functionallyassociated with a non-tangible computer readable storage medium. Thestorage medium stores instructions, which, when executed by theprocessor, carry out actions which control the operation of themechanical and/or electrical components of the capsule. For example, theinstructions may include instructions to activate operation of avibrating agitator at a specific time, frequency, cycle, and/or for aspecific duration. The controller may be functionally associated with,or may include, a transceiver for receiving input, which input may beused to trigger execution of specific instructions stored in the storagemedium.

For the purposes of this application, the term “control unit” refers toa computing circuit or device for controlling operation of mechanicaland/or electrical components of the capsule, which is remote from thecapsule. The control unit includes a processor or processing unitfunctionally associated with a non-tangible computer readable storagemedium. The storage medium stores instructions, which, when executed bythe processor, carry out actions which control the operation of thecapsule or provide instructions to the controller of the capsule. Forexample, the instructions may include instructions to provide to thecapsule a specific vibration protocol or to receive feedback from thecapsule. The control unit is functionally associated with, or includes,a transceiver for communication with the capsule.

For the purposes of this application, the term “clock” relates to amechanism capable of tracking time, in a manner that is indicative of atime of day, for example as a specific hour, minute, and/or secondcombination. The time of day may be relative to a specific time zone,such as Eastern Standard Time (EST) or Greenwich Mean Time (GMT). Aclock may be capable of tracking a time of day relative to a timepreset, by default, by a processor or controller outside of the clock,or by a user, similar to a wrist watch or wall clock set to the time ofday.

For the purposes of this application, the term “timer” relates to amechanism capable of tracking passage of time relative to a beginningtime, and which is not necessarily capable of tracking time in a mannerthat is indicative of a time of day. If the beginning time is indicativeof a time of day, the timer is a clock. In a simple timer, the beginningtime is not indicative of a time of day.

For the purposes of this application, the term “simple timer” relates toa timer, which is not a clock, and is only capable of tracking passageof time in a manner which is not indicative of the time of day. In asimple timer, passage of a specific time duration, such as an hour, willalways be indicated in an identical manner, regardless of differences inthe beginning times. For example, a simple timer tracking an hour from1:14:57 am or tracking an hour from 12:00:00 pm would indicate the samepassage of time—1:00:00—one hour, zero minutes, zero seconds.

Thus, every clock is a timer, but not every timer is a clock.Specifically, a simple timer is not a clock.

For the purposes of this application, the term “predetermined time ofday” relates to any time of day occurring within a specificpredetermined duration. For example, the predetermined time of day 12:00pm to 2:00 pm encompasses any minute or second within the two hoursbetween 12:00 pm and 2:00 pm. Typically, the predetermined time of dayis relative to a specific time zone (e.g., the local time zone where thecapsule is disposed, obtained, programmed, or ingested). As such, thepredetermined time of day 12:00 pm to 2:00 pm EST is different from thepredetermined time of day 12:00 pm to 2:00 pm GMT. The predeterminedtime of day must be predetermined prior to its occurrence, but may bedetermined only shortly before its occurrence. Specifically, thepredetermined time of day need not necessarily be a default time of dayor included in factory settings, and may be computed by a controller orcontrol unit, prior to its arrival.

For the purposes of this application, the term “within”, with respect toa predetermined duration, refers to a period including the predeterminedduration, as well a default “grace period” of up to 45 minutes beforeand after the predetermined duration.

In some embodiments the grace period is 10, 15, 20, or 30 before andafter the predetermined duration.

For the purposes of this application, a vibrating agitator is considered“to operate” at a predetermined duration if it is operative at any pointin time within that predetermined duration.

For the purposes of this application, the term “vibration protocol”relates to a protocol specifying vibration parameters of anintermittently activated vibrating agitator of a vibrating ingestiblecapsule. Typically, the vibration protocol relates to at least one of anactivation time (for a first activation of the vibrating agitator) ofday and an activation delay for initiating vibration (a duration betweenactivation of the capsule and the first activation of the vibratingagitator), a vibration rate (number of vibration cycles per hour), avibration duration and a repose duration for each vibration cycle, avibration frequency, an amount of force exerted by the vibrations, andthe like.

For the purposes of this application, the term “treatment procedure”relates to parameters of a treatment utilizing vibrating ingestiblecapsules, which are typically defined by a treating physician or medicalpractitioner. For example, the treatment procedure may include thenumber of capsules to be taken within a specific time duration (e.g. 3capsules per week, 2 capsules per day), the frequency at which capsulesshould be taken, the time of day at which capsules should be taken,whether the capsule should be taken with or without food, and the like.

For the purpose of this application, the term “treatment protocol”relates to all aspects of treatment of a subject with a vibratingingestible capsule, and includes the treatment procedure as well as thevibration protocol to be used for treating the subject.

For the purpose of this application, the term “activation input” relatesto an input received by a controller of a vibrating ingestible capsule,which causes the controller of the capsule to activate itself, so as tobe able to process inputs and/or to control additional components of thecapsule. The activation input may be received from an element formingpart of the capsule, such as a sensor sensing specific conditions inwhich the capsule should be activated, or from a remote source, such asa remote control unit, for example by way of a signal transmitted to thecapsule, magnetic field applied to the capsule, specific motion appliedto the capsule, or any other type of input provided to the capsule froma remote source.

For the purpose of this application, a vibrating ingestible capsule issaid to be in an “inoperative state” when the capsule is in a storagecondition, intended to preserve the life of a battery thereof. In theinoperative state, components of the capsule which are intended toreceive or to provide an activation input, such as specific sensors,transceivers, and/or timing mechanisms may be active at least to aminimal degree. However, in the inoperative state, no vibration takesplace, and a controller controlling vibration of the capsule isinactive.

For the purpose of this application, a vibrating ingestible capsule issaid to be in an “operative state” when the controller of the capsule isprocessing inputs and data, and can cause a vibrating agitator of thecapsule to vibrate.

For the purpose of this application, the term “jetlag” relates to anysymptom resulting from a change in time zones, including, but notlimited to, a shift in a person's sleep schedule, acute constipationresulting from travel, and the like.

For the purpose of this application, the term “mitigating jetlag”relates to appreciably decreasing any jetlag symptom, for example by atleast 25%. For example, for a traveler who typically suffers from acuteconstipation for the first 48 hours of travel, jetlag would be mitigatedif the traveler suffered from such acute constipation for, at most, thefirst 36 hours of travel.

For the purposes of this application, the term “chronic constipation”relates to a spontaneous bowel movement (SBM) frequency of at most 3SBMs per week,

For the purposes of this application, the term “acute constipation”relates to a subject suffering from a specific event of constipation,without necessarily suffering from chronic constipation. For example,the subject may be constipated for several days following travel, orduring travel, for example as part of the subject's jetlag symptoms.

Referring now to the drawings, FIGS. 1A to 1F are schematic blockdiagrams of various embodiments of gastrointestinal treatment systemsincluding vibrating ingestible capsules according to embodiments of thepresent invention.

As seen in FIG. 1A, a general gastrointestinal treatment system 100includes vibrating ingestible capsule 101. Capsule 101 includes acapsule housing or shell 102, arranged along a longitudinal axis andhaving disposed therein a vibrating agitator 104. A controller 106,which may for example be, or include, a processor, is adapted to controloperation of the vibrating agitator 104, and at least one power source108 provides power to vibrating agitator 104 and controller 106.

Power source 108 may be any suitable power source, such as one or morealkaline or silver oxide batteries, primary batteries, rechargeablebatteries, capacitors and/or supercapacitors.

Intermittently activated vibrating agitator 104 is adapted to have avibration mode of operation (also termed the first mode of operation)and a rest mode of operation (also termed the second mode of operation).In the vibration mode of operation, intermittently activated vibratingagitator 104 is adapted to exert forces on capsule housing 102, suchthat capsule housing 102 exerts vibrations on an environment surroundingcapsule 101.

It is a particular feature of the present invention that controller 106is adapted, in response to receipt of an activation input or when thecapsule is in an operative state, to activate vibrating agitator 104 tooperate in the vibrating mode of operation at at least one predeterminedtime of day, as described in detail hereinbelow with respect to FIGS. 2Ato 2F.

In some embodiments, controller 106 is adapted to activate vibratingagitator 104 to operate in the vibrating mode of operation at the atleast one predetermined time of day, on at least two consecutive days.For example, if controller 106 is adapted to activate vibrating agitator104 to operate in the vibrating mode of operation at 1:00 pm, and thecapsule is ingested by the subject at 6:00 pm on Sunday, controller 106will activate vibrating agitator 104 at 1:00 pm on Monday, and again at1:00 pm on Tuesday. In such embodiments, each activation of thevibrating agitator may be for a predetermined duration, e.g. 2 hours. Insuch embodiments, power source 108 carries sufficient charge foractivation of the vibrating agitator on at least two consecutive days.

In some embodiments, the capsule is in an inoperative state, until thereceipt of an activation input, which causes controller 106 totransition the capsule from the inoperative state to an operative state.

In some embodiments, controller 106 is functionally associated with, orincludes, a timing mechanism 110, powered by power source 108 andadapted to track at least one time characteristic. In some embodiments,the timing mechanism 110 comprises a clock. In some embodiments, thetiming mechanism 110 comprises a timer, for example adapted to track aduration that has passed since an activation input was received, or aduration that has passed since the subject ingested capsule 101.

In some embodiments, in response to receipt of an activation input,controller 106 is adapted to activate operation of a clock timingmechanism 110 to track a time of day, so as to identify the at least onepredetermined time of day for activation of vibration agitator 104.

In some embodiments, capsule 101 is devoid of any sensors for sensing anenvironment thereof, and includes, as timing mechanism 110, a timer. Insome such embodiments, controller 106 is adapted, in response to receiptof an activation input, to wait a predetermined delay time, or a delaytime provided as part of the activation input, and following the delaytime, at a time coinciding with the at least one predetermined time ofday, to activate vibrating agitator 104 to operate in the firstvibration mode of operation.

In other embodiments, such as the embodiment illustrated in FIG. 1 ,capsule 101 further includes at least one sensor 112, functionallyassociated with controller 106. The at least one sensor 112 may beadapted to sense at least one parameter within capsule 101 or in anenvironment of capsule 101, and may include a temperature sensor, anillumination sensor, a moisture sensor, a pressure sensor, anaccelerometer, or any other suitable sensor. In some embodiments, the atleast one sensor 112 is adapted to identify a specific condition incapsule 101 or in the vicinity thereof, and to provide an activationinput to controller 106 in response to identification of the condition.For example, in some embodiments the condition is indicative of thesubject ingesting capsule 101. For example, in some embodiments sensor112 may include an illumination sensor, adapted to identify transitionof capsule 101 from an illuminated environment (e.g. outside the humanbody) to a dark environment (e.g. within the human body) and to providean activation input in response to identification of such a transition.

As another example, in some embodiments sensor 112 may include apressure sensor adapted identify pressure applied to the capsule 101,which pressure is indicative of the capsule moving through a pharynx ofthe subject, and to provide an activation input in response toidentification of such pressure.

As a further example, in some embodiments sensor 112 may include atemperature sensor adapted to identify transition of capsule 101 from anarea with ambient temperature (e.g. outside the human body) to an areawith a human body temperature and to provide an activation input inresponse to identification of such a transition.

As another example, in some embodiments, sensor 112 may include a motionor acceleration sensor, such as an accelerometer, adapted to identify anactivation motion carried out by a user on capsule 101 and to provide anactivation input in response to identification of such a transition. Anexample of an accelerometer providing an activation input for agastrointestinal capsule is provided in U.S. patent application Ser. No.15/168,065 filed on May 29, 2016 (and published as US 2017/0340242),which is incorporated by reference for all purposes as if fully setforth herein.

As a further example, in some embodiments sensor 112 may include amoisture sensor adapted to identify transition of capsule 101 from a dryarea (e.g. outside the human body) to a moist area (e.g. within thehuman body) and to provide an activation input in response toidentification of such a transition.

In some embodiments, such as the embodiment illustrated in FIG. 1A,capsule 101 further includes a location sensor 114, such as a GPS orGLONASS receiver, functionally associated with controller 106. Locationsensor 114 may be adapted to identify the geographic location of thecapsule.

In some embodiments, system 100 further includes a control unit 120,which is typically remote from capsule 101, and which is adapted toprovide one or more inputs to the capsule. In some such embodiments,capsule 101 further includes a remote input receiving mechanism 116,such as a transceiver, functionally associated with controller 106, andadapted to receive inputs from an input providing mechanism 122 ofcontrol unit 120.

In some embodiments, control unit 120 may further include a locationsensor 124, such as a GPS or GLONASS receiver, adapted to identify thegeographic location of the control unit.

In some embodiments, control unit 120 may further include a timingmechanism 126, adapted to track at least one time characteristic, suchas the time of day, or a duration that has passed since a controlinstruction was provided to capsule 101. Typically, the timing mechanism126 comprises a clock.

In some embodiments, control unit 120 may further include a user inputreceiver 128, such as a keyboard, touch screen, or touch pad, adapted toreceive input from a user, such as the subject, a medical professionaltreating the subject, or a caregiver of the subject.

Control unit 120 may be any suitable type of control unit. In someembodiments, control unit may be a suitably configured smart phone or atablet computer.

In some such embodiments, control unit 120 may provide inputs to capsule101 by remotely transmitting the inputs from input providing mechanism122 to remote input receiving mechanism 116, for example using a shortrange wireless communication method, such as radio frequency (RF)communication or Bluetooth® communication. One example of such amechanism for providing input to a capsule is described in U.S. patentapplication Ser. No. 15/132,039 filed Apr. 18, 2016 (and published asUS2017/0296428), and entitled “IN VIVO DEVICE AND METHOD OF USING THESAME”, which is incorporated by reference for all purposes as if fullyset forth herein.

In some embodiments, control unit 120 is adapted to provide theactivation input to controller 106 of capsule 101. In some suchembodiments, control unit 120 provides the activation input prior to thesubject ingesting capsule 101, whereas in other embodiments control unit120 provides the activation input following ingestion of capsule 101 bythe subject.

As discussed hereinabove, controller 106 of capsule 101 is adapted toactivate vibrating agitator 104 to operate in the vibrating mode ofoperation at at least one specific time of day. That specific time ofday may be identified and/or provided to controller 106 by any of anumber of methods or mechanism, some exemplary ones of which aredescribed herein.

In some embodiments, controller 106 of capsule 101 is pre-programmedwith the predetermined time of day, which may be, for example, a defaulttime of day. In such embodiments, timing mechanism 110 of capsule 101comprises a clock, adapted to identify the predetermined time of day.

In some embodiments, capsule 101 is adapted to be used to mitigatejetlag of a user travelling from an origin location having an origintime zone to a destination location having a destination time zone. Insome such embodiments, the pre-determined time of day is a time of dayin the origin time zone. In other such embodiments, the pre-determinedtime of day is a time of day in the destination time zone. In yet otherembodiments, the predetermined time of day is a time of day in a hometime zone, which is the time zone at which the subject normally resides,or has been residing for at least a predetermined duration, for exampleat least one week.

In some such embodiments, timing mechanism 110 provides controller 106with the current time of day, such that, following receipt of theactivation input, or once capsule 101 is in the operative state,controller 106 tracks the current time of day, for example in the origintime zone, the destination time zone, or the home time zone, untilarrival of the predetermined time, and then activates vibrating agitatoraccording to a suitable vibration protocol.

In some embodiments, the predetermined time of day is provided tocontroller 106 as part of the activation input, or in another input, forexample provided by control unit 120.

In some embodiments, regardless of whether the predetermined time of dayis pre-programmed or is provided to controller 106 as an input, theactivation input (or another input) provided to controller 106, forexample by control unit 120, includes the current time of day at thetime of providing the activation input, for example in the origin timezone, the destination time zone, or the home time zone. In suchembodiments, controller 106 and/or timing mechanism 110 is adapted tocompute a delay time from the received current time of day (e.g. thetime of the activation input) to the predetermined time of day, to waitthe computed delay time and subsequently to activate vibrating agitator104 according to a suitable vibration protocol.

In another embodiment, controller 106 may or may not be provided withthe predetermined time of day. However, at the time of providing theactivation input from control unit 120, using timing mechanism 126,control unit 120 computes a time delay between the current time and thepredetermined time of day. Control unit 120 provides an activation inputto controller 106, indicating the computed time delay that controller106 should wait prior to activation of vibrating agitator 104, so thatvibrating agitator 104 will operate in the vibrating mode of operationat the predetermined time of day. Using timing mechanism 110, controller106 waits the computed time delay prior to activation of vibratingagitator, such that the first mode of operation of vibrating agitator104 occurs at the predetermined time of day. In some such embodiments,timing mechanism 110 includes a timer.

In yet another embodiment, at the predetermined time of day, asindicated by timing mechanism 126, control unit 120 identifies that thecurrent time of day is the predetermined time, and provides anactivation input to controller 106 indicating that the vibratingagitator should be activated at this time. Controller 106 is adapted toactivate vibrating agitator 104 to operate in the vibrating mode ofoperation immediately responsive to receipt of such an input. In somesuch embodiments, capsule 101 is devoid of a timing mechanism 110.

In some embodiments, the predetermined time of day is, or coincideswith, at least one predetermined mealtime.

In some such embodiments, the predetermined mealtime is a defaultmealtime. For example, the default mealtime may be a default breakfasttime, which may be between 5 am and 10 am, between 6 am and 10 am,between 6 am and 9 am, between 6 am and 8 am, between 7 am and 10 am,between 7 am and 9 am, and between 7 am and 8 am. As another example,the default mealtime may be a default lunch time, which may be between12 pm and 3 pm, between 12 pm and 2 pm, or between 1 μm and 3 pm. As yetanother example, the default meal time may be a default supper time,which may be between 6 pm and 10 pm, between 7 pm and 10 pm, between Bpmand 10 pm, between 6 pm and 9 pm, between 7 pm and 9 pm, or between 6 pmand 8 pm.

In some embodiments, the at least one predetermined time of day includesat least two predetermined times of day. In some embodiments, the atleast two predetermined times of day include lunchtime. In someembodiments, the at least two predetermined times of day includesuppertime. In some embodiments, the at least two predetermined times ofday include at least two mealtimes. In some embodiments, the at leasttwo mealtimes include lunchtime and suppertime.

In some embodiments, the vibrating agitator is activated at the at leasttwo mealtimes on at least two consecutive days. For example, thevibrating agitator may be activated at lunchtime and suppertime onMonday, and then again at lunchtime and suppertime on Tuesday.

In some embodiments, the vibrating agitator may also be activated anadditional time, at one of the predetermined mealtimes, on a thirdconsecutive day. For example, the vibrating agitator may be activated atlunchtime and suppertime on Monday, again at lunchtime and suppertime onTuesday, and again at lunchtime on Wednesday.

In some embodiments in which the vibrating agitator is activated morethan once, each activation of the vibrating agitator to be in thevibrating mode of operation is for a predetermined duration. Forexample, each activation of the vibrating agitator in the vibrating modeof operation may be for a duration of 1 hour, 1.5 hours, 2 hours, 2.5hours, or 3 hours.

In such embodiments, power source 108 has sufficient charge to enableactivation of the vibrating agitator for the predetermined duration,multiple times. For example, power source 108 may have sufficient chargeto enable activation of the vibrating agitator in the vibrating mode ofoperation for at least 3 times, at least 4 times, or at least 5 times,where each activation is for the predetermined duration.

In some such embodiments, providing the vibration at a specific mealtimetriggers a spontaneous bowel movement (SBM) or a complete spontaneousbowel movement (CSBM) of the subject at a later time of day than thepredetermined time of day. For example, when the vibration is providedat lunchtime, i.e. between 12 pm and 3 pm or between 12 pm and 2 pm, theSBM or CSBM may occur around dinnertime, for example between 6 pm and 9pm.

In some embodiments, use of capsule 101, according to a treatmentprotocol, may increase the number of SBMs experienced by the subject,per week, by at least 1 or at least 2 SBMs.

In some embodiments, use of capsule 101, according to a treatmentprotocol, may increase the number of CSBMs experienced by the subject,per week, by at least 1 or at least 2 CSBMs.

In some embodiments, the predetermined time of day is a user-specifictime of day, or a user-specific mealtime at which the subject typicallyeats his/her meals. In some such embodiments, user input receiver 128 ofcontrol unit 120 (or an input receiver forming part of capsule 101 (notshown)), is adapted to receive, from the user (e.g. the subject or acaregiver of the subject) information about the user-specific time ofday or user-specific mealtime. Control unit 120 may then provide theuser-specific time of day or the user-specific mealtime to controller106, for example as part of an activation input or as a separate input,or may provide a suitable input or activation input based on theuser-specific time of day or the user-specific mealtime. For example, ifthe subject is used to eating their meals at 11 am and 4 pm, these timesmay be provided as input to control unit 120, which may then communicatethese predetermined times of day to controller 106 for activation ofvibrating agitator 104 at these times, or otherwise ensures thatcontroller 106 will activate the vibrating agitator at these times, forexample by indicating a suitable delay time or providing an activationinput at the user-specific time of day or the user-specific mealtime, asexplained hereinabove. As another example, if the subject wishes for thecapsule to vibrate at 4:00 am, the subject may provide this informationas input to control unit 120, which may then communicate thispredetermined time to controller 106 for activation of vibratingagitator 104 at this time.

In some embodiments, the predetermined time of day is suited to thegeographic region in which the capsule, the control unit 120, or thesubject, are located. For example, if the subject has ingested thecapsule, and has changed time zones since ingesting the capsule (forexample flew from New-York to Chicago), the predetermined time of daymay be adjusted to correspond to the new time zone in which the user islocated. In some embodiments, the predetermined time of day is aregion-specific mealtime at which the people in a geographical region atwhich the subject (or capsule) is located typically eat their meals.

The times at which people typically have supper, or dinner, may varygreatly between different geographical regions. For example, in the U.S.typical supper times are between 5 pm and Bpm or between 6 pm and 8 pm,whereas in Argentina most people only eat their supper between 9 pm and11 pm, or even as late as midnight. Thus, the geographical region inwhich the capsule (and the subject) is located, may be used to identifythe typical mealtimes of the subject.

In some such embodiments, location sensor 114 of capsule 101 mayidentify the location of the capsule, and provide the location or aregion of the location to controller 106. In other embodiments, locationsensor 124 of control unit 120 may identify the location of the controlunit, and may provide the location or a region of the location tocontroller 106 as part of the activation input or as part of anotherinput. Controller 106 may then determine the predetermined time of day,or region-specific mealtime, at which the vibrating agitator 104 shouldbe in the operative mode of operation, based on the region. For example,controller 106 may be preprogrammed with predetermined times of day forspecific regions, and may select a suitable pre-programmed predeterminedtime of day based on the identified region. As another example,controller 106 may access a database (not shown) to find theregion-specific time of day, or region-specific mealtimes, for theidentified region.

In yet other embodiments, location sensor 124 of control unit 120 mayidentify the location of the control unit, and may obtain, based on theidentified location, the region-specific predetermined time(s) of day orregion-specific mealtime(s), for example by accessing a pre-programmedlist or by accessing a database (not shown). Control unit 120 may thenprovide the obtained region-specific predetermined time(s) of day tocontroller 106, substantially as described hereinabove. Alternatively,control unit 120 may provide activation inputs, based on the obtainedregion-specific predetermined time(s) of day, to the controller 106,without providing the region-specific predetermined time(s) of day tothe controller, substantially as described hereinabove.

In some embodiments, in which the capsule 101 is adapted to mitigatejetlag, the predetermined time of day is suited to the geographic regionfrom which the capsule, the control unit 120, or the subject, originate,or to the origin time zone of the subject. For example, if the subjecthas ingested the capsule, and has changed time zones since ingesting thecapsule (for example flew from New-York to Chicago), the predeterminedtime of day is preferably maintained at the origin time zone of theorigin location of the subject.

In some embodiments, the predetermined time of day is suited to thegeographic region at which the capsule, the control unit 120, or thesubject, arrive, or to the destination time zone of the subject. Forexample, if the subject has ingested the capsule, and has changed timezones since ingesting the capsule (for example flew from New-York toChicago), the predetermined time of day is preferably maintained at thedestination time zone at which the subject has arrived.

In some embodiments, the capsule is adapted to operate in multiplecycles and/or during multiple predetermined times of day. In some suchembodiments, in a first cycle or predetermined time of day, the time issuited to the geographic region from which the capsule, the control unit120, or the subject, originate, or to the origin time zone of thesubject, and in a second cycle or predetermined time of day, the time issuited to the geographic region at which the capsule, the control unit120, or the subject, arrive, or to the destination time zone of thesubject.

In some embodiments, the predetermined time of day is suited to thecircadian cycle of the user, or to a default circadian cycle. Forexample, the predetermined time of day may be one occurring apredetermined duration prior to, or near, a time that, according to thecircadian cycle, the user is likely to have a bowel movement, such thatoperation of the capsule 101 may “assist” the gastrointestinal tract ingenerating, or completing, such a bowel movement. Additional examplesrelating to the circadian cycle are described hereinbelow with respectto FIG. 3 . In some embodiments, the predetermined time of day may beselected to be a time of day at which the gastric pH of the user isrelatively high, as explained in further detail hereinbelow with respectto FIG. 4 .

In some embodiments, controller 106 only activates vibrating agitator104 in the vibrating mode of operation at the predetermined time, ifsome minimum threshold duration has passed since capsule 101 wasactivated to be in the operative state, since receipt of the activationinput, or since the user ingested the capsule. For example, the capsulemay be pre-programmed such that controller 106 is adapted to activatevibrating agitator in the vibrating mode of operation from 6 am to 8 am,and from 6 pm to 8 pm, and the minimum threshold duration is four hoursfrom ingestion of the capsule. If the subject ingests the capsule at 12pm on Sunday, controller 106 would cause vibrating agitator 104 tooperate in the vibrating mode of operation at 6 pm on Sunday, since thepredetermined time of 6 pm is six hours following ingestion. However, ifthe subject ingests the capsule at 5 pm on Sunday, controller 106 wouldcause vibrating agitator 104 to operate in the vibrating mode ofoperation only at 6 am on Monday, since the first predetermined time of6 pm is fewer than four hours following ingestion. Such a thresholdduration may be particularly useful when it is desired that the capsulevibrate in a specific region or portion of the gastrointestinal tract,so that the delay time is required for the capsule to reach the specificregion.

Relating to the characteristics of vibrating agitator 104, the vibratingagitator may be any suitable mechanism that can be intermittentlyactivated and can apply suitable forces onto capsule housing 102.

In some embodiments, intermittently activated vibrating agitator 104 mayinclude a radial agitator adapted to exert radial forces on capsulehousing 102, in a radial direction with respect to the longitudinal axisof housing 102. For example, the radial agitator may include anunbalanced weight attached to a shaft of an electric motor powered by abattery or by power source 108, substantially as described in U.S. Pat.No. 9,707,150, which is incorporated by reference for all purposes as iffully set forth herein.

In some embodiments, intermittently activated vibrating agitator 104 mayinclude an axial agitator adapted to exert radial forces on the capsulehousing 102, in an axial direction with respect to a longitudinal axisof housing 102. For example, the axial agitator may include an electricmotor powered by a battery or by power source 108, and an urgingmechanism, associated with, and driven by, the electric motor, such thatthe urging mechanism adapted to exert said axial forces, substantiallyas described in U.S. Pat. No. 9,707,150. In some embodiments, the urgingmechanism is adapted to exert the axial forces in opposite directions.In some embodiments, the urging mechanism is adapted to deliver at leasta portion of the axial forces in a knocking mode.

In some embodiments, the forces exerted by intermittently activatedvibrating agitator 104 on capsule housing 102 in the vibration mode ofoperation include radial forces in a radial direction with respect tothe longitudinal axis of the housing and axial forces in an axialdirection with respect to the longitudinal axis. In some embodiments, asingle agitator exerts both the radial and the axial forces. In otherembodiments, the axial forces are exerted by one agitator, and theradial forces are exerted by another, separate, agitator, where bothagitators form part of intermittently activated vibrating agitator 104.

In some embodiments, the intermittently activated vibrating agitator 104may include a magnet mounted onto a rotor adapted to exert a magneticfield as well as radial forces on capsule housing 102. For example, sucha magnetic vibrating agitator is described in U.S. patent applicationSer. No. 15/058,216 filed on Mar. 2, 2016 (and published as US2016/0310357), and entitled “PHYSIOTHERAPY DEVICE AND METHOD FORCONTROLLING THE PHYSIOTHERAPY DEVICE”, which is incorporated byreference for all purposes as if fully set forth herein.

In some embodiments, housing 102 may include first and second members,and vibrating agitator 104 may include a mechanism adapted to effect avibration by moving the first member of the housing in the oppositedirection relative to the second member of the housing, substantially asdescribed in U.S. Pat. No. 9,078,799, which is incorporated by referencefor all purposes as if fully set forth herein.

In the vibrating mode of operation, intermittently activated vibratingagitator 104 is adapted to have a plurality of vibration cycles, whereeach cycle includes a vibration duration followed by a repose duration.Forces are exerted by the vibrating agitator 104 on capsule housing 102only during the vibration duration, and as such capsule housing 102 onlyexerts forces on an environment thereof during the vibration duration.

In some embodiments, the number of vibration cycles per hour is in therange of 20 to 400, 40 to 400, 60 to 400, 80 to 400, 40 to 380, 60 to380, 80 to 380, 40 to 360, 60 to 360, 80 to 360, 100 to 360, 100 to 330,100 to 300, 100 to 280, 100 to 250, 100 to 220, 100 to 200, 120 to 300,120 to 280, 120 to 250, 120 to 220, 120 to 200, 150 to 300, 150 to 280,150 to 250, 150 to 220, 150 to 200, 170 to 300, 170 to 250, 170 to 220,or 170 to 200.

In some embodiments, the repose duration is greater than the vibrationduration.

In some embodiments, the vibration duration is in the range of 0.1second to 10 seconds, 1 second to 10 seconds, 1 second to 9 seconds, 2seconds to 9 seconds, 3 seconds to 9 seconds, 3 seconds to 8 seconds, 3seconds to 7 seconds, 3 seconds to 6 seconds, or 4 seconds to 6 seconds.

In some embodiments, the repose duration is in the range of 1 second to180 seconds, 3 seconds to 180 seconds, 5 seconds to 180 seconds, 5seconds to 150 seconds, 5 seconds to 120 seconds, 8 seconds to 100seconds, 8 seconds to 30 seconds, 10 seconds to 80 seconds, 10 secondsto 70 seconds, 10 seconds to 60 seconds, 10 seconds to 50 seconds, 10seconds to 40 seconds, 10 seconds to 30 seconds, 10 seconds to 20seconds, or 15 seconds to 20 seconds.

In some embodiments, the total duration of one vibration cycle is in therange of 1.1 seconds to 200 seconds, 5 seconds to 200 seconds, 10seconds to 200 seconds, 10 seconds to 150 seconds, 10 seconds to 100seconds, 10 seconds to 80 seconds, 10 seconds to 50 seconds, 10 secondsto 40 seconds, 10 seconds to 30 seconds, 15 seconds to 50 seconds, 15seconds to 40 seconds, 15 seconds to 30 seconds, or 15 seconds to 25seconds.

In some embodiments, the cumulative duration of the vibrating mode ofoperation, or the cumulative duration during which vibration cycles areoccurring, is in the range of 1 hour to 12 hours, 2 hours to 10 hours, 2hours to 8 hours, 2 hours to 6 hours, 2 hours to 4 hours, or 2 hours to3 hours. It will be appreciated that the cumulative duration ofvibration cycles may be dependent on properties of power source 108.

It will be appreciated by persons skilled in the art that the vibrationmode of operation may be intermittent, or interrupted, such thatvibrating agitator 104 is operative in the vibration mode for a firstduration, for example 30 minutes, then does not have any vibrationcycles for a second duration, for example 1 hour, and then is operativein the vibration mode of operation and has vibration cycles for a thirdduration, for example two hours. The cumulative duration relates to thesum of all durations during which vibrating agitator 104 was operativein the vibration mode of operation and included vibration cycles,including the vibration duration and the repose duration of eachvibration cycle.

In some embodiments, vibrating agitator 104 is configured to exertforces on the capsule housing 102, such that a net force exerted by thecapsule housing 102 on the environment thereof is in the range of 50grams force (gf) to 600 gf, 50 gf to 550 gf, 100 gf to 550 gf, 100 gf to500 gf, 150 gf to 500 gf, 200 gf to 500 gf, or 200 gf to 450 gf.

In some embodiments, vibrating agitator 104 is configured to exert saidforces on capsule housing 102 to attain a capsule housing 102vibrational frequency within a range of 10 Hz to 650 Hz, 15 Hz to 600Hz, 20 Hz to 550 Hz, 30 Hz to 550 Hz, 50 Hz to 500 Hz, 70 Hz to 500 Hz,100 Hz to 500 Hz, 130 Hz to 500 Hz, or 150 Hz to 500 Hz.

It will be appreciated that the exact specifications of the capsule,such as the specific frequency and force ranges applicable to a specificcapsule, are dependent on the specifications of the power source and ofthe vibrating agitator.

It will be further appreciated that a specific capsule may be controlledby the controller such that different vibrational frequencies may beattained and/or different net forces may be exerted, by the capsule indifferent vibration cycles of the capsule. Due to the naturaldistinction between subjects, use of multiple different parameters indifferent vibration cycles of a single capsule would allow the capsuleto successfully treat multiple subjects, even if the personal optimaltreatment for those subjects is not the same, as there is a higherchance that in at least some of the vibration cycles the activationparameters of the capsule would reach, or be close to, the optimalparameters for each specific subject.

Controller 106 is adapted to control the operation of intermittentlyactivated vibrating agitator 104. Such control may include control ofany one or more of the force applied by the vibrating agitator, thevibrational frequency reached, the times in which vibrating agitator 104operates in the vibration mode of operation, the vibration duration ofeach vibration cycle, the repose duration of each vibration cycle, thevibration cycle duration, and cumulative vibration duration of thevibrating agitators.

In some embodiments, controller 106 is adapted to receive informationrelating to the desired vibration protocol from control unit 120, priorto ingestion of the capsule or to activation thereof, or during thecapsule's traversal of the subject's GI tract. For example, theinformation may be remotely transmitted from control unit 120 tocontroller 106, for example using a short range wireless communicationmethod. In some embodiments, the information is transmitted as a list ofvibration parameters for effecting the vibration protocol. In someembodiments, the information is transmitted as executable code foreffecting the first vibration protocol.

In some embodiments, the information includes one or more of at leastone predetermined time of day, a time delay from receipt of theinformation to the at least one predetermined time of day, a region inwhich the control unit is located, a desired number of vibration cycles,a desired vibration duration in each vibration cycle, a desired reposeduration in each vibration cycle, a desired cumulative vibrationduration, and the like.

In some embodiments, controller 106 is adapted to control vibratingagitator 104 so that the capsule applies forces to an environmentthereof to effect a mechanical stimulation of the wall of thegastrointestinal tract of the subject at the predetermined time(s) ofday.

Turning to FIG. 1B, in one embodiment, the gastrointestinal treatmentsystem includes only a vibrating ingestible capsule 101 b. Capsule 101 bincludes a capsule housing or shell 102, arranged along a longitudinalaxis and having disposed therein a vibrating agitator 104. Capsule 101 bfurther includes a controller 106 b, which may for example be, orinclude, a processor, is adapted to control operation of the vibratingagitator 104, and at least one power source 108 provides power tovibrating agitator 104 and controller 106 b.

Shell 102, vibrating agitator 104, and power source 108, are allsubstantially as described hereinabove with respect to FIG. 1A.

Capsule 101 b further includes a clock 110 b, and at least one sensor112, both functionally associated with controller 106 b and both poweredby power source 108.

The at least one sensor 112 is adapted to sense at least one parameterwithin capsule 101 b or in an environment of capsule 101 b, to identifya specific condition in capsule 101 b or in the vicinity thereof, and toprovide an activation input to controller 106 in response toidentification of the condition. Typically, the condition is indicativeof the subject ingesting capsule 101 b. Examples of suitable sensors andconditions are provided hereinabove with respect to FIG. 1A.

It is a particular feature of the embodiment of FIG. 1B that controller106 b is preprogrammed with at least one predetermined time of day aswell as with a vibration protocol, as discussed hereinabove. Controller106 b is adapted, in response to receiving from sensor(s) 112 anindication that the capsule has been ingested, to activate clock 110 bto track the time of day, so as to identify occurrence of the at leastone preprogrammed predetermined time of day, and to activate vibratingagitator 104 to operate in the vibrating mode of operation, inaccordance with the preprogrammed vibration protocol, at the at leastone preprogrammed predetermined time of day.

In some embodiments, the capsule is in an inoperative state, until thereceipt of the sensor indication, which causes controller 106 b totransition the capsule from the inoperative state to an operative state.

The at least one preprogrammed predetermined time of day is typically atleast one default time of day, which may be, or may coincide with, atleast one default mealtime, as described hereinabove with respect toFIG. 1A. As discussed hereinabove, a bowel movement supported by ortriggered by the vibration may occur at a later time than thepredetermined time of day.

As discussed hereinabove, the at least one time of day may include atleast two predetermined times of day, such as two mealtimes. In someembodiments, the vibrating agitator may operate in the vibrating mode ofoperation at the at least one, or at least two, predetermined times ofday, in two or more consecutive days.

In some embodiments, the at least one preprogrammed predetermined timeof day is suited to a default circadian cycle, for example of a personwho is awake during the day and sleeps during the night. For example,the predetermined time of day may be one occurring a predeterminedduration prior to a time that, according to the default circadian cycle,a subject is likely to have a bowel movement, such that operation of thecapsule 101 b may “assist” the gastrointestinal tract in generating, orcompleting, such a bowel movement. Additional examples relating to thecircadian cycle are described hereinbelow with respect to FIG. 3 .

In some embodiments, the clock 110 b may be set to a default time zone,for example a time zone at the location capsule 101 b is sold orprovided. In such embodiments, the controller 106 b will be adapted toactivate vibrating agitator 104 to operate in the vibrating mode ofoperation at the preprogrammed predetermined time of day when thatoccurs in the default time zone, regardless of the actual location ofthe capsule. For example, if a subject received capsule 101 b from aphysician in New York, the clock 110 b will be set to EST. If thesubject then travels to London, and ingests the capsule in London, thecapsule will still vibrate at the predetermined time of day according toEST, and not according to GMT.

In other embodiments, capsule 101 b further includes a location sensor114, such as a GPS or GLONASS receiver, functionally associated withcontroller 106 b, which is adapted to identify the geographic locationof the capsule. In some such embodiments, when the user travels from anorigin time zone to a destination time zone (such as from EST to GMT, asin the previous example), the location sensor 114 provides to controller106 b an indication of the change in time zone, and controller 106 b mayreset clock 110 b to the destination time zone, or may otherwisecompensate for the change in time zone, such that the vibration willoccur at the preprogrammed predetermined time of day in accordance withthe destination time zone.

As discussed hereinabove with respect to FIG. 1A, in some embodiments,controller 106 b only activates vibrating agitator 104 in the vibratingmode of operation at the preprogrammed predetermined time(s), if someminimum threshold duration has passed since controller 106 b received anindication of ingesting of capsule 101 b.

Turning to FIG. 1C, in one embodiment, the gastrointestinal treatmentsystem 100 c which includes a vibrating ingestible capsule 101 c, aswell as a control unit 120 c. Capsule 101 c includes a capsule housingor shell 102, arranged along a longitudinal axis and having disposedtherein a vibrating agitator 104. Capsule 101 c further includes acontroller 106 c, which may for example be, or include, a processor, isadapted to control operation of the vibrating agitator 104, and at leastone power source 108 provides power to vibrating agitator 104 andcontroller 106 c.

Shell 102, vibrating agitator 104, and power source 108, are allsubstantially as described hereinabove with respect to FIG. 1A.

Capsule 101 c further includes a clock 110 c and a remote inputreceiving mechanism 116, such as a transceiver, both powered by powersource 108.

In the embodiment of FIG. 1C, controller 106 c is preprogrammed with atleast one predetermined time of day as well as with a vibrationprotocol, as discussed hereinabove. However, capsule 101 c has no meansfor identifying when it has been ingested, for the controller 106 c tobegin its operation.

Control unit 120 c, includes an input providing mechanism 122, such as atransceiver, adapted to provide an activation input to transceiver 116of capsule 101 c. Typically, the activation input is provided fromcontrol unit 120 c to controller 106 c when the subject places thecapsule 101 c on the control unit 120 c, operates a specific program orapplication on control unit 120 c, or otherwise indicates to controlunit 120 c that he is about to ingest the capsule. The subject typicallyingests the capsule immediately following provision of the activationinput.

In some embodiments, control unit 120 c further includes a user inputreceiver (an input interface) 128 via which the subject, or a caretakerthereof, may provide an indication that the subject is about to ingestthe capsule 101 c.

Control unit 120 c, transceiver 122, and user input receiver 128, may besubstantially as described hereinabove with respect to FIG. 1A.

In some embodiments, control unit 120 c is devoid of a timing mechanism.

Controller 106 c is adapted, in response to receipt of the activationinput from control unit 120 c, to activate clock 110 c to track the timeof day, so as to identify occurrence of the at least one preprogrammedpredetermined time of day, and to activate vibrating agitator 104 tooperate in the vibrating mode of operation, in accordance with thepreprogrammed vibration protocol, at the at least one preprogrammedpredetermined time of day.

In some embodiments, the capsule is in an inoperative state, until thereceipt of the activation input, which causes controller 106 c totransition the capsule from the inoperative state to an operative state.

The at least one preprogrammed predetermined time of day is typically atleast one default time of day, which may be, or may coincide with, atleast one default mealtime, as described hereinabove with respect toFIG. 1A. As discussed hereinabove, a bowel movement supported by ortriggered by the vibration may occur at a later time than thepredetermined time of day.

As discussed hereinabove, the at least one time of day may include atleast two predetermined times of day, such as two mealtimes. In someembodiments, the vibrating agitator may operate in the vibrating mode ofoperation at the at least one, or at least two, predetermined times ofday, in two or more consecutive days.

In some embodiments, the at least one preprogrammed predetermined timeof day is suited to a default circadian cycle, for example of a personwho is awake during the day and sleeps during the night. For example,the predetermined time of day may be one occurring a predeterminedduration prior to a time that, according to the default circadian cycle,a subject is likely to have a bowel movement, such that operation of thecapsule 101 c may “assist” the gastrointestinal tract in generating, orcompleting, such a bowel movement. Additional examples relating to thecircadian cycle are described hereinbelow with respect to FIG. 3 .

In some embodiments, the clock 110 c may be set to a default time zone,for example a time zone at the location capsule 101 c is sold orprovided. In such embodiments, the controller 106 c will be adapted toactivate vibrating agitator 104 to operate in the vibrating mode ofoperation at the preprogrammed predetermined time of day when thatoccurs in the default time zone, regardless of the actual location ofthe capsule. For example, if a subject received capsule 101 c from aphysician in New York, the clock 110 c will be set to EST. If thesubject then travels to London, and ingests the capsule in London, thecapsule will still vibrate at the predetermined time of day according toEST, and not according to GMT.

In other embodiments, capsule 101 c further includes a location sensor114, such as a GPS or GLONASS receiver, functionally associated withcontroller 106 c, which is adapted to identify the geographic locationof the capsule. In some such embodiments, when the user travels from anorigin time zone to a destination time zone (such as from EST to GMT, asin the previous example), the location sensor 114 provides to controller106 c an indication of the change in time zone, and controller 106 c mayreset clock 110 c to the destination time zone, or may otherwisecompensate for the change in time zone, such that the vibration willoccur at the preprogrammed predetermined time of day in accordance withthe destination time zone.

As discussed hereinabove with respect to FIG. 1A, in some embodiments,controller 106 c only activates vibrating agitator 104 in the vibratingmode of operation at the preprogrammed predetermined time(s), if someminimum threshold duration has passed since controller 106 c receivedthe activation input.

Turning now to FIG. 1D, the embodiment of FIG. 1D is substantiallysimilar to that of FIG. 1C. The main difference between the embodimentof FIGS. 1C and 1D is that in the embodiment of FIG. 1D thegastrointestinal capsule is not preset with the predetermined time(s) ofday, and receives these as part of the activation input, from thecontrol unit.

As seen in FIG. 1D, the gastrointestinal treatment system 100 d whichincludes a vibrating ingestible capsule 101 d, as well as a control unit120 d. Capsule 101 d includes a capsule housing or shell 102, arrangedalong a longitudinal axis and having disposed therein a vibratingagitator 104. Capsule 101 d further includes a controller 106 d, whichmay for example be, or include, a processor, is adapted to controloperation of the vibrating agitator 104, and at least one power source108 provides power to vibrating agitator 104 and controller 106 d.

Shell 102, vibrating agitator 104, and power source 108, are allsubstantially as described hereinabove with respect to FIG. 1A.

Capsule 101 d further includes a clock 110 d and a remote inputreceiving mechanism 116, such as a transceiver, both powered by powersource 108.

Control unit 120 d, includes an input providing mechanism 122, such as atransceiver, adapted to provide an activation input to transceiver 116of capsule 101 d. The activation input includes at least onepredetermined time of day at which the capsule 101 d should be operativein the vibrating mode of operation. In some embodiments, the activationinput may further include a vibration protocol, substantially asdiscussed hereinabove with respect to FIG. 1A.

Typically, the activation input is provided from control unit 120 d tocontroller 106 d when the subject places the capsule 101 d on thecontrol unit 120 d, operates a specific program or application oncontrol unit 120 d, or otherwise indicates to control unit 120 d that heis about to ingest the capsule. The subject typically ingests thecapsule immediately following provision of the activation input.

In some embodiments, control unit 120 d further includes a user inputreceiver (an input interface) 128 via which the subject, or a caretakerthereof, may provide an indication that the subject is about to ingestthe capsule 101 d.

Control unit 120 d, may further include a timing mechanism 126 which istypically a clock, and may, in some embodiments, include a locationsensor 124, as explained in further detail herein. Control unit 120 d,transceiver 122, clock 126, location sensor 124, and user input receiver128, may be substantially as described hereinabove with respect to FIG.1A.

In some embodiments, the at least one predetermined time of day may bepreset or preprogrammed in the control unit 120 d. In some embodiments,the at least one time of day may be a default time of day, which may be,or may coincide with, at least one default mealtime, as describedhereinabove with respect to FIG. 1A.

As discussed hereinabove, the at least one time of day may include atleast two predetermined times of day, such as two mealtimes. In someembodiments, the vibrating agitator may operate in the vibrating mode ofoperation at the at least one, or at least two, predetermined times ofday, in two or more consecutive days.

In other embodiments, the control unit 120 d may be adapted to computeor otherwise determine the at least one predetermined time of day.

In some such embodiments, the control unit 120 d may determine thepredetermined time(s) of day based on a geographical location of thecontrol unit, for example as identified by the location sensor 124, asdescribed hereinabove with respect to FIG. 1A.

In other such embodiments, the control unit 120 d may determine thepredetermined time(s) of day based on user input received via user inputreceiver via user input receiver 128. In some embodiments, the controlunit 120 d determines the time(s) of day is suited to the user'scircadian cycle, for example based on a sleep schedule and/or based on ameal schedule provided as part of the user input. For example, thepredetermined time of day may be one occurring a predetermined durationprior to a time that, according to the default circadian cycle, asubject is likely to have a bowel movement, such that operation of thecapsule 101 d may “assist” the gastrointestinal tract in generating, orcompleting, such a bowel movement. Additional examples relating to thecircadian cycle are described hereinbelow with respect to FIG. 3 .

Controller 106 d is adapted, in response to receipt of the activationinput from control unit 120 d, to activate clock 110 d to track the timeof day, so as to identify occurrence of the at least one predeterminedtime of day received as part of the activation input, and to activatevibrating agitator 104 to operate in the vibrating mode of operation, inaccordance with a preprogrammed vibration protocol or a vibrationprotocol received as part of the activation input, at the at least onepredetermined time of day.

In some embodiments, the capsule is in an inoperative state, until thereceipt of the activation input, which causes controller 106 d totransition the capsule from the inoperative state to an operative state.

In some embodiments, the clock 110 d may be set to a default time zone,for example a time zone at the location capsule 101 d is sold orprovided. In some such embodiments, the controller 106 d will be adaptedto activate vibrating agitator 104 to operate in the vibrating mode ofoperation at the predetermined time of day when that occurs in thedefault time zone, regardless of the actual location of the capsule. Forexample, if a subject received capsule 101 d from a physician in NewYork, the clock 110 d will be set to EST. If the subject then travels toLondon, and ingests the capsule in London, the capsule will stillvibrate at the predetermined time of day according to EST, and notaccording to GMT.

In other embodiments, when providing the activation input, control unit120 d may use clock 126 and location sensor 124 thereof to compensatefor the change in time zone, such that the time of day provided tocontroller 106 d is corrected to match the time zone at which thecontrol unit is currently located.

In yet other embodiments, capsule 101 d further includes a locationsensor 114, such as a GPS or GLONASS receiver, functionally associatedwith controller 106 d, which is adapted to identify the geographiclocation of the capsule. In some such embodiments, when the user travelsfrom an origin time zone to a destination time zone (such as from EST toGMT, as in the previous example), the location sensor 114 provides tocontroller 106 d an indication of the change in time zone, andcontroller 106 d may reset clock 110 d to the destination time zone, ormay otherwise compensate for the change in time zone, such that thevibration will occur at the predetermined time of day in accordance withthe destination time zone.

As discussed hereinabove with respect to FIG. 1A, in some embodiments,controller 106 d only activates vibrating agitator 104 in the vibratingmode of operation at the predetermined time(s), if some minimumthreshold duration has passed since controller 106 d received theactivation input (which is indicative of the subject planning to ingestthe capsule).

Turning now to FIG. 1E, the embodiment of FIG. 1E is substantiallysimilar to that of FIG. 1D. The main difference between the embodimentof FIGS. 1D and 1E is that in the embodiment of FIG. 1E the activationinput does not include the predetermined time of day, but ratherincludes a time delay, from the current time, to the predetermined timeof day.

As seen in FIG. 1E, the gastrointestinal treatment system 100 e whichincludes a vibrating ingestible capsule 101 e, as well as a control unit120 e. Capsule 101 e includes a capsule housing or shell 102, arrangedalong a longitudinal axis and having disposed therein a vibratingagitator 104. Capsule 101 e further includes a controller 106 e, whichmay for example be, or include, a processor, is adapted to controloperation of the vibrating agitator 104, and at least one power source108 provides power to vibrating agitator 104 and controller 106 e.

Shell 102, vibrating agitator 104, and power source 108, are allsubstantially as described hereinabove with respect to FIG. 1A.

Capsule 101 e further includes a timer 110 e and a remote inputreceiving mechanism 116, such as a transceiver, both powered by powersource 108.

Control unit 120 e, includes an input providing mechanism 122, such as atransceiver, adapted to provide an activation input to transceiver 116of capsule 101 e. The activation input includes at least one delay time,from a current time of day to at least one predetermined time of day atwhich the capsule 101 e should be operative in the vibrating mode ofoperation. In some embodiments, the activation input may further includea vibration protocol, substantially as discussed hereinabove withrespect to FIG. 1A.

Typically, the activation input is provided from control unit 120 e tocontroller 106 e when the subject places the capsule 101 e on thecontrol unit 120 e, operates a specific program or application oncontrol unit 120 e, or otherwise indicates to control unit 120 e that heis about to ingest the capsule. The subject typically ingests thecapsule immediately following provision of the activation input.

In some embodiments, control unit 120 e further includes a user inputreceiver (an input interface) 128 via which the subject, or a caretakerthereof, may provide an indication that the subject is about to ingestthe capsule 101 e.

Control unit 120 e, further includes a timing mechanism 126 which istypically a clock, and may, in some embodiments, include a locationsensor 124, as explained in further detail herein. Control unit 120 e,transceiver 122, clock 126, location sensor 124, and user input receiver128, may be substantially as described hereinabove with respect to FIG.1A.

In some embodiments, the at least one predetermined time of day may bepreset or preprogrammed in the control unit 120 e. In some embodiments,the at least one time of day may be a default time of day, which may be,or may coincide with, at least one default mealtime, as describedhereinabove with respect to FIG. 1A.

As discussed hereinabove, the at least one time of day may include atleast two predetermined times of day, such as two mealtimes. In someembodiments, the vibrating agitator may operate in the vibrating mode ofoperation at the at least one, or at least two, predetermined times ofday, in two or more consecutive days.

In other embodiments, the control unit 120 e may be adapted to computeor otherwise determine the at least one predetermined time of day.

In some such embodiments, the control unit 120 e may determine thepredetermined time(s) of day based on a geographical location of thecontrol unit, for example as identified by the location sensor 124, asdescribed hereinabove with respect to FIG. 1A.

In other such embodiments, the control unit 120 e may determine thepredetermined time(s) of day based on user input received via user inputreceiver via user input receiver 128. In some embodiments, the controlunit 120 e determines the time(s) of day is suited to the user'scircadian cycle, for example based on a sleep schedule and/or based on ameal schedule provided as part of the user input. For example, thepredetermined time of day may be one occurring a predetermined durationprior to a time that, according to the default circadian cycle, asubject is likely to have a bowel movement, such that operation of thecapsule 101 e may “assist” the gastrointestinal tract in generating, orcompleting, such a bowel movement. Additional examples relating to thecircadian cycle are described hereinbelow with respect to FIG. 3 .

Controller 106 e is adapted, in response to receipt of the activationinput from control unit 120 e, to activate timer 110 e to track passageof time until completion of the delay time, and to activate vibratingagitator 104 to operate in the vibrating mode of operation, inaccordance with a preprogrammed vibration protocol or a vibrationprotocol received as part of the activation input, at a time coincidingwith the at least one predetermined time of day.

In some embodiments, the capsule is in an inoperative state, until thereceipt of the activation input, which causes controller 106 e totransition the capsule from the inoperative state to an operative state.

In other embodiments, when providing the activation input, control unit120 e may use clock 126 and location sensor 124 thereof to compensatefor a change in time zone, such as would be caused by a user travellingfrom New York to London, such that the delay time provided to controller106 e is corrected so that the vibration will occur at the predeterminedtime of day in the destination location, or at which the subject iscurrently located.

As discussed hereinabove with respect to FIG. 1A, in some embodiments,controller 106 e only activates vibrating agitator 104 in the vibratingmode of operation following the delay time, if some minimum thresholdduration has passed since controller 106 e received the activation input(which is indicative of the subject planning to ingest the capsule).

It is a particular feature of the embodiment of FIG. 1E that, althoughthe capsule 101 e is not (necessarily) aware of the time of day, thecontrol unit controls the capsule such that the vibrating mode ofoperation occurs at the predetermined time(s) of day.

Turning now to FIG. 1F, the embodiment of FIG. 1F is distinct from theembodiments of FIGS. 1B to 1E in that the activation input is providedat the predetermined time of day, after the user has ingested thegastrointestinal capsule.

As seen in FIG. 1F, the gastrointestinal treatment system 100 f whichincludes a vibrating ingestible capsule 101 f, as well as a control unit120 f. Capsule 101 f includes a capsule housing or shell 102, arrangedalong a longitudinal axis and having disposed therein a vibratingagitator 104. Capsule 101 f further includes a controller 106 f, whichmay for example be, or include, a processor, is adapted to controloperation of the vibrating agitator 104, and at least one power source108 provides power to vibrating agitator 104 and controller 106 f.

Shell 102, vibrating agitator 104, and power source 108, are allsubstantially as described hereinabove with respect to FIG. 1A.

Capsule 101 f further includes a remote input receiving mechanism 116,such as a transceiver, powered by power source 108. Transceiver 116 issufficiently strong, or uses a suitable protocol, such that transceiver116 can receive communications from outside the body, while capsule 101f traverses the GI tract.

Capsule 101 f is devoid of a timing mechanism.

Control unit 120 f, includes an input providing mechanism 122, such as atransceiver, adapted to communicate and to provide an activation inputto transceiver 116 of capsule 101 f, even following ingestion of thecapsule. The activation input indicates to the controller 106 f that thevibrating agitator should be operated in the first vibrating mode ofoperation now, at the time of receipt of the activation input. In someembodiments the activation input may include the vibration protocol tobe used, substantially as described hereinabove with respect to FIG. 1A,and/or the duration for which the capsule should vibrate, in response tothe activation input.

In some embodiments, a link between the capsule 101 f and the controlunit 120 f may be formed when the subject places the capsule 101 f onthe control unit 120 f, prior to ingestion of the capsule.

Control unit 120 f, further includes a timing mechanism 126 which istypically a clock, and may, in some embodiments, include a locationsensor 124, as explained in further detail herein. Control unit 120 f,transceiver 122, clock 126, location sensor 124, and user input receiver128, may be substantially as described hereinabove with respect to FIG.1A.

In some embodiments, the at least one predetermined time of day may bepreset or preprogrammed in the control unit 120 f. In some embodiments,the at least one time of day may be a default time of day, which may be,or may coincide with, at least one default mealtime, as describedhereinabove with respect to FIG. 1A.

As discussed hereinabove, the at least one time of day may include atleast two predetermined times of day, such as two mealtimes. In someembodiments, the vibrating agitator may be activated, e.g. by thecontrol unit, operate in the vibrating mode of operation at the at leastone, or at least two, predetermined times of day, in two or moreconsecutive days.

In other embodiments, the control unit 120 f may be adapted to computeor otherwise determine the at least one predetermined time of day.

In some such embodiments, the control unit 120 f may determine thepredetermined time(s) of day based on a geographical location of thecontrol unit, for example as identified by the location sensor 124, asdescribed hereinabove with respect to FIG. 1A.

In other such embodiments, the control unit 120 f may determine thepredetermined time(s) of day based on user input received via user inputreceiver via user input receiver 128. In some embodiments, the controlunit 120 f determines the time(s) of day is suited to the user'scircadian cycle, for example based on a sleep schedule and/or based on ameal schedule provided as part of the user input. For example, thepredetermined time of day may be one occurring a predetermined durationprior to a time that, according to the default circadian cycle, asubject is likely to have a bowel movement, such that operation of thecapsule 101 f may “assist” the gastrointestinal tract in generating, orcompleting, such a bowel movement. Additional examples relating to thecircadian cycle are described hereinbelow with respect to FIG. 3 .

Following ingestion of the capsule, when control unit 120 f determinesthat the predetermined time of day has arrived, for example by trackingtime using clock 126, it provides an activation input to controller 106f. Controller 106 f is adapted, in response to receipt of the activationinput from control unit 120 f, to activate vibrating agitator 104 tooperate in the vibrating mode of operation, in accordance with apreprogrammed vibration protocol or a vibration protocol received aspart of the activation input, at a time coinciding with the at least onepredetermined time of day.

In some embodiments, the capsule is in an inoperative state, until thelinking of the capsule and the control unit, which causes controller 106f to transition the capsule from the inoperative state to an operativestate.

It is a particular feature of the embodiment of FIG. 1F that, althoughthe capsule 101 f is not aware of the time of day, the control unitcontrols the capsule such that the vibrating mode of operation occurs atthe predetermined time(s) of day.

Reference is now additionally made to FIGS. 2A to 2F, which areschematic flowcharts of embodiments of methods for treating thegastrointestinal tract according to the present invention, the treatmentbeing based on use of the gastrointestinal treatment system of FIGS. 1Ato 1F, respectively. For example, the methods of treatment illustratedin FIGS. 2A to 2F may be used for treating an ailment of thegastrointestinal tract, or for mitigating jetlag of the user.

It will be appreciated by people of skill in the art that the methodsdescribed herein may be used for treatment of various ailments of thegastrointestinal tract, including constipation, a sensation of strainingwhile defecating, a sensation of gastric bloating, diarrhea, andgastroparesis.

It will further be appreciated by people of skill in the art that themethods described herein may be used for mitigating at least an acuteconstipation symptom of jetlag of a subject.

Turning to FIG. 2A, it is seen that at step 200, initially the treatmentprotocol for the subject is determined, for example by a treatingphysician or medical practitioner. The treatment protocol may indicatethe number of treatment sessions per week or per other time duration,the time of day at which a capsule should be ingested, one or morepredetermined times of day at which the capsule should be operative,and/or may indicate the vibration protocol of the capsule.

In some embodiments, for example when the treatment is intended tomitigate jetlag of a travelling subject, the treatment protocol may beselected at least partially according to a travel plan of the subject.As such, the treatment protocol may take into consideration, forexample, times the subject will be in travelling (e.g. on an airplane,boat, or train), the origin time zone (from which the subject will beleaving), the destination time zone (at which the subject will bearriving), and the time of day at which the subject will be arriving atthe destination.

At step 202, a controller 106 of an ingestible capsule 101 is providedwith a predetermined time, or times, of day at which the vibratingagitator should be operated in the vibrating mode of operation. In someembodiments the controller is also provided with the number ofconsecutive days that the vibrating agitator should be operated in thevibrating mode of operation, at the predetermined time(s). In someembodiments, the controller may also be provided with a specification ofa time zone to which the predetermined time(s) of day should relate, forexample an origin time zone or a destination time zone of a travellingsubject.

In some embodiments, at step 204 controller 106 may optionally receive,or be programmed with, a desired vibration protocol for the subject.

At step 206, the capsule may be activated for use, by transitioning thecapsule from an inoperative state to an operative state, for example byreceipt of an activation input.

The subject ingests the capsule at step 208, and at step 210 controller106 control vibrating agitator 104 such that the vibrating mode ofoperation occurs at the predetermined time(s) of day, for the definednumber of consecutive days.

In some embodiments, providing of the predetermined time(s) at step 202and/or providing the desired vibration protocol for the subject at step204 occurs at the time of manufacturing of the capsule, for example bypre-programming the time(s) into the controller.

In some embodiments, providing of the predetermined time(s) at step 202and/or providing the desired vibration protocol for the subject at step204 may be effected by a control unit, such as control unit 120 of FIG.1A.

For example, control unit 120 may provide to controller 106 thepredetermined time of day, a user-specific predetermined time of day, aregion-specific predetermined time of day, or a time-zone specific timeof day as described hereinabove. In such embodiments, step 202 may becarried out at any time prior to operating to the vibrating agitator inthe vibrating mode of operation at step 210, and specifically may becarried out prior to ingestion of the capsule by the subject, orfollowing the subject ingesting the capsule.

For example, the programming of the vibration protocol and/or of thepredetermined time of day may include remotely transmitting the desiredvibration protocol and/or predetermined time of day from the controlunit 120 to the controller 106, for example using a short-range wirelesscommunication method. In some embodiments, the desired vibrationprotocol is transmitted as a list of vibration parameters for effectingthe vibration protocol. In some embodiments, the desired vibrationprotocol is transmitted as executable code for effecting the vibrationprotocol.

In some embodiments, the control unit provides the predetermined time ofday to controller 106 at the predetermined time of day, which isequivalent to giving the command “operate the vibrating agitator 104now”. In such embodiments, step 202 is carried out following the subjectingesting the capsule at step 208.

As mentioned above, the capsule is activated for use at step 206.Typically, the capsule is activated by receipt of an activation input.

As discussed hereinabove, in some embodiments the activation input maybe received from the control unit 120 or from sensors within the capsulesensing that the capsule has been ingested or that a user has carriedout an activation motion with the capsule.

In some embodiments, the capsule is activated prior to the useringesting the capsule at step 208, for example by a signal from thecontrol unit or by the user carrying out an activation motion. In otherembodiments, the activation input is provided at the time of ingestionor immediately thereafter, for example by sensors sensing a change inthe environment of the capsule due to its ingestion, as described atlength hereinabove.

In yet other embodiments, the activation input may be provided remotelywhen the capsule is already in the body of the subject, for example byremote communication from control module 120.

Following activation of capsule 101, or together therewith, capsule 101is ingested by the subject, and begins to travel through thegastrointestinal tract of the subject, as seen at step 208.

Operation of vibrating agitator 104 in the vibrating mode of operationat step 210 effects vibration of capsule housing 102, as describedhereinabove, such that the housing exerts vibrations on the environmentsurrounding the capsule. Specifically, vibration of capsule housing 102may be intended to effect a mechanical stimulation of the wall of thegastrointestinal tract at the predetermined time of day.

In some embodiments, vibration of the capsule at the predetermined timeof day, which effects the mechanical stimulation, triggers the subjectto have an SBM or a CSBM at a later time of day than the vibration. Forexample, vibration of the capsule between 12 pm and 2 pm may trigger thesubject to have a CSBM between 6 pm and 8 pm. In some embodiments, forexample when the method of FIG. 2A is used to treat an ailment of thegastrointestinal tract, a treatment session as defined in steps 202 to210 may be repeatedly administered to the subject as specified in thetreatment protocol for the subject, determined or obtained at step 200.In some embodiments, the treatment protocol includes administering aplurality of treatment sessions to the subject. In some embodiments, thetreatment protocol includes administering at least one treatment sessionto the subject per week, over a treatment period of at least two weeks,at least at least three weeks, at least four weeks, at least five weeks,at least six weeks, or at least eight weeks. In some embodiments, thetreatment protocol includes administering 1 to 7 treatment sessions perweek, 3 to 14 treatment sessions per two weeks, 2 to 7 treatmentsessions per week, 5 to 14 treatment sessions per two weeks, 3 to 7treatment sessions per week, 7 to 14 treatment sessions per two weeks, 4to 7 treatment sessions per week, or 5 to 7 treatment sessions per week.

Turning now to FIG. 2B, it is seen that at step 200 b, initially thetreatment procedure for the subject may be determined, for example by atreating physician or medical practitioner. The treatment procedure mayindicate the number of treatment sessions per week or per other timeduration and/or the time of day at which a capsule should be ingested.

At step 202 b, the subject obtains a vibrating ingestible capsule, forexample capsule 101 b as described hereinabove with respect to FIG. 1B.A controller 106 b of the capsule is preprogrammed with a predeterminedtime, or times, of day at which the vibrating agitator should beoperated in the vibrating mode of operation, with the number ofconsecutive days that the capsule should be operated in the vibratingmode of operation at the predetermined time(s), and with a vibrationprotocol for the vibrating mode of operation.

The subject ingests the capsule at step 208. Upon ingestion of thecapsule, sensor 112 of capsule 101 b provides to controller 106 b aninput indicating that the capsule has been ingested, and the controllertrack time and activates vibrating agitator 104 such that the vibratingmode of operation occurs at the predetermined time(s) of day. Operationof vibrating agitator 104 in the vibrating mode of operation effectsvibration of capsule housing 102, as described hereinabove, such thatthe housing exerts vibrations on the environment surrounding thecapsule. Specifically, vibration of capsule housing 102 may be intendedto effect a mechanical stimulation of the wall of the gastrointestinaltract at the predetermined time of day.

In some embodiments, vibration of the capsule at the predetermined timeof day, which effects the mechanical stimulation, triggers the subjectto have an SBM or a CSBM at a later time of day than the vibration. Forexample, vibration of the capsule between 12 pm and 2 pm may trigger thesubject to have a CSBM between 6 pm and 8 pm.

In some embodiments, for example when the method of FIG. 2B is used totreat an ailment of the gastrointestinal tract, a treatment session asdefined in steps 202 b and 208 may be repeatedly administered to thesubject as specified in the treatment procedure for the subject,determined or obtained at step 200 b. In some embodiments, the treatmentprocedure includes administering a plurality of treatment sessions tothe subject, substantially as described hereinabove with respect to FIG.2B.

Turning now to FIG. 2C, it is seen that at step 200 c, initially thetreatment procedure for the subject may be determined, for example by atreating physician or medical practitioner. The treatment procedure mayindicate the number of treatment sessions per week or per other timeduration and/or the time of day at which a capsule should be ingested.

At step 202 c, the subject obtains a vibrating ingestible capsule, forexample capsule 101 c as described hereinabove with respect to FIG. 1C.A controller 106 c of the capsule is preprogrammed with a predeterminedtime, or times, of day at which the vibrating agitator should beoperated in the vibrating mode of operation, with the number ofconsecutive days that the capsule should be operated in the vibratingmode of operation at the predetermined time(s), and with a vibrationprotocol for the vibrating mode of operation.

At step 206 c, the subject causes a control unit, distinct from thecapsule, such as control unit 120 c of FIG. 1C, to provide an activationinput to the capsule 101 c. For example, the subject (or a caregiverthereof) may place the capsule in or on the control unit for apredetermined duration, so as to provide the activation input from thecontrol unit to the capsule. As another example, the subject may operatean application running on the control unit, or otherwise provide a userinput to the control unit, so as to trigger the control unit to send anactivation input to the capsule.

Following provision of the activation input at step 206 c, the subjectingests the capsule at step 208. Upon receipt of the activation inputfrom control unit 120 c (and regardless of actual ingestion of thecapsule), controller 106 c tracks time and activates vibrating agitator104 such that the vibrating mode of operation occurs at thepredetermined time(s) of day. Operation of vibrating agitator 104 in thevibrating mode of operation effects vibration of capsule housing 102, asdescribed hereinabove, such that the housing exerts vibrations on theenvironment surrounding the capsule. Specifically, vibration of capsulehousing 102 may be intended to effect a mechanical stimulation of thewall of the gastrointestinal tract at the predetermined time of day.

In some embodiments, vibration of the capsule at the predetermined timeof day, which effects the mechanical stimulation, triggers the subjectto have an SBM or a CSBM at a later time of day than the vibration. Forexample, vibration of the capsule between 12 pm and 2 pm may trigger thesubject to have a CSBM between 6 pm and 8 pm.

In some embodiments, for example when the method of FIG. 2C is used totreat an ailment of the gastrointestinal tract, a treatment session asdefined in steps 202 c to 208 may be repeatedly administered to thesubject as specified in the treatment procedure for the subject,determined or obtained at step 200 c. In some embodiments, the treatmentprocedure includes administering a plurality of treatment sessions tothe subject, substantially as described hereinabove with respect to FIG.2C.

Turning now to FIG. 2D, it is seen that at step 200 d, initially thetreatment protocol for the subject is determined, for example by atreating physician or medical practitioner. The treatment protocol mayindicate the number of treatment sessions per week or per other timeduration, the time of day at which a capsule should be ingested, one ormore predetermined times of day at which the capsule should beoperative, a number of consecutive days that the capsule should beoperated in the vibrating mode of operation at the predeterminedtime(s), and/or may indicate the vibration protocol of the capsule.Typically, at least a portion of the treatment protocol is provided tothe control unit, such as control unit 120 d of FIG. 1D.

At step 202 d, the subject obtains, or is provided, a vibratingingestible capsule, for example capsule 101 d as described hereinabovewith respect to FIG. 1D. In some embodiments, the capsule may beprovided by a medical practitioner, such as a treating physician.

At step 206 d, the subject causes the control unit, to provide anactivation input to the capsule 101 d. The activation input includes theat least one time of day at which the capsule should operate in thevibrating mode of operation, and in some embodiments may also includethe number of consecutive days that the capsule should be operated inthe vibrating mode of operation at the predetermined time(s), and/or thevibration protocol as determined at step 200 d. For example, the subject(or a caregiver thereof) may place the capsule in or on the control unitfor a predetermined duration, so as to provide the activation input fromthe control unit to the capsule. As another example, the subject mayoperate an application running on the control unit, or otherwise providea user input to the control unit, so as to trigger the control unit tosend an activation input to the capsule.

Following provision of the activation input at step 206 d, the subjectingests the capsule at step 208. Upon receipt of the activation inputfrom control unit 120 d (and regardless of actual ingestion of thecapsule), controller 106 c tracks time and activates vibrating agitator104 such that the vibrating mode of operation occurs at thepredetermined time(s) of day received with the activation input.Operation of vibrating agitator 104 in the vibrating mode of operationeffects vibration of capsule housing 102, as described hereinabove, suchthat the housing exerts vibrations on the environment surrounding thecapsule. Specifically, vibration of capsule housing 102 may be intendedto effect a mechanical stimulation of the wall of the gastrointestinaltract at the predetermined time of day.

In some embodiments, vibration of the capsule at the predetermined timeof day, which effects the mechanical stimulation, triggers the subjectto have an SBM or a CSBM at a later time of day than the vibration. Forexample, vibration of the capsule between 12 pm and 2 pm may trigger thesubject to have a CSBM between 6 pm and 8 pm.

In some embodiments, at optional step 203 d, a user input may bereceived at the control unit, for example via a user interface thereof.For example, the user input may include information pertaining to thecircadian cycle of the subject, such as the subject's sleep scheduleand/or meal schedule. The user input may be provided by the subject,medical personnel, or by a caregiver of the subject. The user input maybe used to set, or to adjust, the predetermined time(s) of day for thesubject.

In some embodiments, the predetermined time(s) of day is preset in thecontrol unit, or is determined at step 200 d and is provided to thecontrol unit.

In other embodiments, at optional step 204 d, the control unit computesthe predetermined time(s) of day, prior to providing the activationinput to the capsule. The computation may be based on user inputreceived at step 203 d or on a location of the control unit asidentified by location sensor 124.

In some embodiments, for example when the method of FIG. 2D is used totreat an ailment of the gastrointestinal tract, a treatment session asdefined in steps 202 d to 208 may be repeatedly administered to thesubject as specified in the treatment procedure for the subject,determined or obtained at step 200 d. In some embodiments, the treatmentprocedure includes administering a plurality of treatment sessions tothe subject, substantially as described hereinabove with respect to FIG.2D.

Turning now to FIG. 2E, it is seen that at step 200 e, initially thetreatment protocol for the subject is determined, for example by atreating physician or medical practitioner. The treatment protocol mayindicate the number of treatment sessions per week or per other timeduration, the time of day at which a capsule should be ingested, one ormore predetermined times of day at which the capsule should beoperative, a number of consecutive days that the capsule should beoperated in the vibrating mode of operation at the predeterminedtime(s), and/or may indicate the vibration protocol of the capsule.Typically, at least a portion of the treatment protocol is provided tothe control unit, such as control unit 120 e of FIG. 1E.

At step 202 e, the subject obtains, or is provided, a vibratingingestible capsule, for example capsule 101 e as described hereinabovewith respect to FIG. 1E. In some embodiments, the capsule may beprovided by a medical practitioner, such as a treating physician.

At step 206 e, the subject causes the control unit, to provide anactivation input to the capsule 101 e. The activation input includes atleast one-time delay from a current time to at least one time of day atwhich the capsule should operate in the vibrating mode of operation, andin some embodiments may also include the number of consecutive days thatthe capsule should be operated in the vibrating mode of operation at thepredetermined time(s), and/or the vibration protocol as determined atstep 200 e. The at least one-time delay may be computed by the controlunit, based on the current time and the predetermined time(s) of day.For example, the subject (or a caregiver thereof) may place the capsulein or on the control unit for a predetermined duration, so as to providethe activation input from the control unit to the capsule. As anotherexample, the subject may operate an application running on the controlunit, or otherwise provide a user input to the control unit, so as totrigger the control unit to send an activation input to the capsule.

Following provision of the activation input at step 206 e, the subjectingests the capsule at step 208. Upon receipt of the activation inputfrom control unit 120 e (and regardless of actual ingestion of thecapsule), controller 106 e tracks passage of time until the at least onetime delay has been completed, and activates vibrating agitator 104 tooperate in the vibrating mode of operation, such that the vibrating modeof operation coincides with the predetermined time(s) of day. Operationof vibrating agitator 104 in the vibrating mode of operation effectsvibration of capsule housing 102, as described hereinabove, such thatthe housing exerts vibrations on the environment surrounding thecapsule. Specifically, vibration of capsule housing 102 may be intendedto effect a mechanical stimulation of the wall of the gastrointestinaltract at the predetermined time of day.

In some embodiments, vibration of the capsule at the predetermined timeof day, which effects the mechanical stimulation, triggers the subjectto have an SBM or a CSBM at a later time of day than the vibration. Forexample, vibration of the capsule between 12 pm and 2 pm may trigger thesubject to have a CSBM between 6 pm and 8 pm.

In some embodiments, at optional step 203 e, a user input may bereceived at the control unit, for example via a user interface thereof.For example, the user input may include information pertaining to thecircadian cycle of the subject, such as the subject's sleep scheduleand/or meal schedule. The user input may be provided by the subject,medical personnel, or by a caregiver of the subject. The user input maybe used to set, or to adjust, the predetermined time(s) of day for thesubject.

In some embodiments, the predetermined time(s) of day is preset in thecontrol unit, or is determined at step 200 e and is provided to thecontrol unit.

In other embodiments, at optional step 204 e, the control unit computesthe predetermined time(s) of day, as well as the delay time(s), prior toproviding the activation input to the capsule. The computation of thepredetermined time(s) of day may be based on user input received at step203 e or on a location of the control unit as identified by locationsensor 124.

In some embodiments, for example when the method of FIG. 2E is used totreat an ailment of the gastrointestinal tract, a treatment session asdefined in steps 202 e to 208 may be repeatedly administered to thesubject as specified in the treatment procedure for the subject,determined or obtained at step 200 e. In some embodiments, the treatmentprocedure includes administering a plurality of treatment sessions tothe subject, substantially as described hereinabove with respect to FIG.2E.

Turning now to FIG. 2F, it is seen that at step 200 f, initially thetreatment protocol for the subject may be determined, for example by atreating physician or medical practitioner. The treatment protocol mayindicate the number of treatment sessions per week or per other timeduration, the time of day at which a capsule should be ingested, one ormore predetermined times of day at which the capsule should beoperative, a number of consecutive days that the capsule should beoperated in the vibrating mode of operation at the predeterminedtime(s), and/or may indicate the vibration protocol of the capsule.Typically, at least a portion of the treatment protocol is provided tothe control unit, such as control unit 120 f of FIG. 1F.

At step 202 f, the subject obtains, or is provided, a vibratingingestible capsule, for example capsule 101 f as described hereinabovewith respect to FIG. 1F. In some embodiments, the capsule may beprovided by a medical practitioner, such as a treating physician.

The subject ingests the capsule at step 208.

Subsequently, at step 210 f, at the at least one predetermined time ofday, the control unit 120 f provides an activation input to the capsule101 f. In some embodiments, the activation input may include thevibration protocol as determined at step 200 f. Upon receipt of theactivation input from control unit 120 f, controller 106 f,substantially immediately, activates vibrating agitator 104 to operatein the vibrating mode of operation, such that the vibrating mode ofoperation coincides with the predetermined time(s) of day. Operation ofvibrating agitator 104 in the vibrating mode of operation effectsvibration of capsule housing 102, as described hereinabove, such thatthe housing exerts vibrations on the environment surrounding thecapsule. Specifically, vibration of capsule housing 102 may be intendedto effect a mechanical stimulation of the wall of the gastrointestinaltract at the predetermined time of day.

In some embodiments, providing the activation input at step 210 f isresponsive to a user input. In other embodiments, providing theactivation input at step 210 f is automatic, and is based on controlunit 120 f knowing the predetermined time(s) of day, and tracking timeusing clock 126 to identify the arrival of the predetermined time(s) ofday.

In some embodiments, vibration of the capsule at the predetermined timeof day, which effects the mechanical stimulation, triggers the subjectto have an SBM or a CSBM at a later time of day than the vibration. Forexample, vibration of the capsule between 12 pm and 2 pm may trigger thesubject to have a CSBM between 6 pm and 8 pm.

In some embodiments, at optional step 203 f, a user input may bereceived at the control unit, for example via a user interface thereof.For example, the user input may include information pertaining to thecircadian cycle of the subject, such as the subject's sleep scheduleand/or meal schedule. The user input may be provided by the subject,medical personnel, or by a caregiver of the subject. The user input maybe used to set, or to adjust, the predetermined time(s) of day for thesubject.

In some embodiments, the predetermined time(s) of day is preset in thecontrol unit, or is determined at step 200 f and is provided to thecontrol unit.

In other embodiments, at optional step 204 f, the control unit computesthe predetermined time(s) of day, prior to providing the activationinput(s) to the capsule. The computation of the predetermined time(s) ofday may be based on user input received at step 203 f or on a locationof the control unit as identified by location sensor 124. In someembodiments, for example when the method of FIG. 2F is used to treat anailment of the gastrointestinal tract, a treatment session as defined insteps 202 f to 210 f may be repeatedly administered to the subject asspecified in the treatment procedure for the subject, determined orobtained at step 200 f. In some embodiments, the treatment procedureincludes administering a plurality of treatment sessions to the subject,substantially as described hereinabove with respect to FIG. 2F.

Reference is now made to FIG. 3 , which is a schematic illustration ofthe circadian cycle of a person, including suitable times of day for theimplementation of the methods of FIGS. 2A to 2F. The times of day shownin FIG. 3 , and the corresponding body activities or characteristics atthose times of day, are known in the art, and have been shown in medicaland scientific research.

As will be noted, according to the typical circadian cycle shown in FIG.3 , a bowel movement is likely around 8:30 am, and bowel movements aresuppressed around 10:30 pm (22:30).

As shown in the Examples below, Applicants have discovered that settinga vibrating ingestible capsule, such as the capsule describedhereinabove with respect to FIG. 1 , to vibrate during the morning hours(e.g. around 7:00-8:00 am) significantly increases the number of SBMsexperienced by users in those hours.

Without wishing to be bound by theory, Applicants surmise that vibrationduring the morning hours, at which bowel movements are likely accordingto the circadian cycle, affects the walls of the gastrointestinal tractand promotes peristaltic movement, thereby assisting in completion ofthe bowel movement the body is likely to be promoting at that time. Asshown in the Examples below, Applicants have further discovered thatsetting a vibrating ingestible capsule, such as the capsule describedhereinabove with respect to FIG. 1 , to vibrate during the evening hours(e.g. around 7:00-9:00 pm) significantly increases the number of SBMsexperienced by users in those hours and/or in the morning hours, whenthe gastrointestinal system “wakes up”.

Without wishing to be bound by theory, Applicants surmise that vibrationduring the evening hours, prior to the body suppressing bowel movementsaccording to the circadian cycle, affects the walls of thegastrointestinal tract and promotes peristaltic movement, therebyassisting in creating an additional bowel movement “cleaning out” the GItract before bowel movements are suppressed, and/or that the triggeredperistaltic movement which assists in generating an SBM or CSBM in themorning hours.

Without wishing to be bound by theory, the Applicants further surmisethat when the gastrointestinal tract is sufficiently active withcontractions suitable for generating an SBM or a CSBM, such as duringthe morning hours or during breakfast time, any impact of the vibrationsof the capsule is small relative to the contractions already occurring.The Applicants further surmise that when the digestive system isinactive, for example not during mealtimes, vibrations of the capsuleare insufficient to generate peristaltic activity of thegastrointestinal tract. However, when the digestive system is active,but typically not enough to generate a bowel movement, activation of thecapsule may “assist” the gastrointestinal tract in completing a bowelmovement, resulting in an increase in the number of bowel movements theuser experiences during a predefined duration, e.g. per week. Referenceis now made to FIG. 4 , which is a graphic illustration of the gastricpH of a person, indicating suitable times of day for the implementationof the methods of FIGS. 2A and 2F.

As seen in FIG. 4 , the gastric pH of a typical person oscillates duringthe day, and is relatively high at typical mealtimes, and then decreasesgradually until the next mealtime. Research has shown gastric pH issensed by mechanoreceptors in the GI tract, and is tied to peristalsisin the GI tract (see for example “Acid sensing in the gastrointestinaltract” to Holtzer, (Am J Physiol Gastrointest Liver Physiol. 2007 March;292(3): G699-G705, https://www.ncbi.nlmnih.gov/pmc/articles/PMC4370835/) in the section aboutEsophago-gastro-duodenal motility).

As shown in the Examples below, Applicants have discovered that settinga vibrating ingestible capsule, such as the capsule describedhereinabove with respect to FIG. 1 , to vibrate during typical mealtimes(during the morning hours and during the evening hours) significantlyincreases the number of SBMs experienced by users in those hours, or ina few hours following vibration.

Without wishing to be bound by theory, Applicants surmise that vibrationat mealtimes, at which there are changes in the gastric pH according tothe graph provided in FIG. 4 , and during which times there is likely tobe peristaltic activity in the GI tract, impacts the walls of thegastrointestinal tract and supports the peristaltic movement, therebyassisting in promoting bowel movements at those times.

EXAMPLES

Reference is now made to the following examples, which, together withthe above description, illustrates the invention in a non-limitingfashion.

Example 1

A study which included 130 participating subjects suffering fromconstipation was conducted. Half of the participating subjects, termedherein “trial subjects”, were treated with a vibrating gastrointestinalcapsule according to a treatment protocol, in accordance with thepresent invention, while the other half, termed herein “sham subjects”,were treated with a sham capsule, which appeared and behaved identicallyto the vibrating gastrointestinal capsule prior to ingesting thereof,but did not vibrate within the subject's alimentary tract.

The treatment protocol included treatment cycles including administeringone gastrointestinal capsule per day five times per week, repeated for atreatment duration of six weeks. The administered capsules included anon-chargeable battery as the power source, and a coin-type eccentricvibration motor as the vibrating agitator.

The capsules administered to the “trial subjects” were programmed tohave operate in the vibration mode of operation during the morning hoursfollowing an activation time delay of at least 8 hours, and when in thevibration mode of operation, to have vibration treatment cyclesincluding a 3 second vibration duration followed by a 16 second reposeduration, for a cumulative treatment duration of 1.5 to 3 hours. Duringthe vibration mode of operation, the force applied by the capsulehousing on the surrounding environment was in the range of 200gram-force to 500 gram-force, and the vibrational frequency was in therange of 120 Hz to 280 Hz. Different specific forces were applied to thesurrounding environment, and corresponding different vibrationalfrequencies were attained, in different vibration cycles of theadministered capsules.

Due to the activation time delay, it is assumed that vibration wasaffected when the capsules were disposed in a section of the largeintestine of the participating subjects.

The results of the study are shown in FIG. 5A, which illustrates thepercentage of complete spontaneous bowel movements (CSBMs) relative to atime from ingestion of the capsules. As seen in FIG. 5A, at the timeswhen vibration of the capsules is effected—between 8 and 11 hours afteringestion of the capsules and during the morning hours, the subjectsreceiving active capsules had a significantly greater number of CSBMsthan those receiving sham capsules. As such, the results illustrated inFIG. 5A indicate that vibration of the capsules in the morning hours(e.g. at times at which bowel movements are likely according to thecircadian cycle), and/or coinciding with mealtimes (e.g. at times atwhich gastric pH is low), improves the success of the treatment—therebyproviding motivation for treating subjects at specific times of day.

Example 2

A study which included 26 participating subjects suffering fromconstipation was conducted. 16 of the participating subjects, termedherein “trial subjects”, were treated with a vibrating gastrointestinalcapsule according to a treatment protocol, in two different arms of thestudy, in accordance with the present invention, while the remaining tensubjects, termed herein “sham subjects”, were treated with a shamcapsule, which appeared and behaved identically to the vibratinggastrointestinal capsule prior to ingesting thereof, but did not vibratewithin the subject's alimentary tract.

The treatment protocol included treatment cycles including administeringone gastrointestinal capsule per day five times per week, repeated for atreatment duration of six weeks. The administered capsules included anon-chargeable battery as the power source, and a coin-type eccentricvibration motor as the vibrating agitator.

The capsules administered to the “trial subjects” were programmed tohave operate in the vibration mode of operation during the early morninghours following an activation time delay of at least 8 hours, and tooperate in the vibration mode of operation again during the afternoonhours. The capsules were programmed, when in the vibration mode ofoperation, to have vibration treatment cycles including a 3 secondvibration duration followed by a 16 second repose duration, for acumulative treatment duration of 1.5 to 3 hours. During the vibrationmode of operation, the force applied by the capsule housing on thesurrounding environment was in the range of 200 gram-force to 500gram-force, and the vibrational frequency was in the range of 120 Hz to280 Hz. Different specific forces were applied to the surroundingenvironment, and corresponding different vibrational frequencies wereattained, in different vibration cycles of the administered capsules.

Due to the activation time delay, it is assumed that vibration wasaffected when the capsules were disposed in a section of the largeintestine of the participating subjects.

The results of the study are shown in FIG. 5B, which illustrates thepercentage of complete spontaneous bowel movements (CSBMs) relative to atime from ingestion of the capsules. As seen in FIG. 5B, at the timeswhen vibration of the capsules is effected—between 8 and 11 am, andbetween 7 and 9 pm, the subjects receiving active capsules had asignificantly greater number of CSBMs than those receiving shamcapsules. As such, the results illustrated in FIG. 5B indicate thatimprovement of the subject's symptoms of the subject's symptoms byaddition of CSBMs is coincidental with times at which the capsulevibrates, thus demonstrating the efficacy of the capsules, and thebenefit in activating the capsules to operate at specific times of day,which coincide with mealtimes and/or at which the circadian cycleindicates that a bowel movement is likely and prior to bowel movementsbecoming unlikely according to the circadian cycle.

Example 3

A study was conducted, which study included 299 participating subjectssuffering from chronic idiopathic constipation according to the Rome IIIcriteria and who have not experienced relief of their symptoms fromavailable therapies. 155 of the participating subjects, termed herein“trial subjects”, were treated with a vibrating gastrointestinal capsuleaccording to a treatment protocol, in accordance with the presentinvention, while the remaining 144 subjects, termed herein “placebosubjects”, were treated with a placebo capsule, which appearedidentically to the vibrating gastrointestinal capsule prior to ingestingthereof, but disintegrated within the subject's alimentary tract.

All subjects were observed and monitored for two weeks, termed a “run-inperiod”. During the run-in period, the subjects were asked to refrainfrom taking any medication or supplement to relieve their constipation.The subjects completed a diary every day, in which the subjects reportedregarding their daily bowel movements, change of diet, change ofsymptoms, and change in general health conditions. The run in period wasused to set a baseline for the number of SBMs, and CSBMs that eachsubject experiences per week.

During the trial period, subjects continued to complete the diary, andto report their experience regarding daily bowel movements, as well asregarding straining and consistency of bowel movements (in accordancewith the Bristol stool scale).

The treatment protocol included treatment cycles including administeringone gastrointestinal capsule per day five times per week, repeated for atreatment duration of eight weeks. The administered capsules included anon-chargeable battery as the power source, and a coin-type eccentricvibration motor as the vibrating agitator.

The capsules administered to the “trial subjects” were programmed tooperate in the vibration mode of operation at two predetermined times ofday, for approximately two hours each time, for a total of fivevibration periods.

The capsules administered to the “trial subjects” were programmed tooperate in the vibration mode of operation during lunchtime and againduring suppertime, for three consecutive days. As such, each capsulevibrated during lunchtime and supper time on day 1, during lunchtime andsuppertime on day 2, and during lunchtime on day 3, if the capsule wasstill in the gastrointestinal tract of the user.

The capsules were programmed, when in the vibration mode of operation,to have vibration treatment cycles including a 3 second vibrationduration followed by a 16 second repose duration, for a cumulativetreatment duration of 1.5 to 3 hours. During the vibration mode ofoperation, the force applied by the capsule housing on the surroundingenvironment was in the range of 200 gram-force to 500 gram-force, andthe vibrational frequency was in the range of 120 Hz to 280 Hz.Different specific forces were applied to the surrounding environment,and corresponding different vibrational frequencies were attained, indifferent vibration cycles of the administered capsules.

The capsules were programmed to vibrate only following an activationtime delay of at least 8 hours. Due to the activation time delay, it isassumed that vibration was affected when the capsules were disposed in asection of the large intestine of the participating subjects.

The capsules were programmed to vibrate for multiple consecutive days.Additionally, capsules were administered to the subjects five days perweek, i.e. on some consecutive days. Consequently, there were times atwhich multiple capsules simultaneously operated in the vibration mode ofoperation within the gastrointestinal tract of a subject, at differentlocations along the gastrointestinal tract.

Results of the study, with respect to number of bowel movements, areshown in Table 1.

TABLE 1 Trial subjects Placebo Result n N % n N % p-value At least 1additional 63 155 40.65 33 144 22.92 <0.0001 CSBM for at least 6 out of8 weeks At least 2 additional 36 155 23.23 17 144 11.81 0.0008 CSBM forat least 6 out of 8 weeks

The results of the study with respect to number of bowel movements arefurther shown in FIGS. 6A and 6B. FIG. 6A illustrates the per-weekproportion of subjects who had one additional CSBM relative to thebaseline, for at least six out of eight weeks. FIG. 6B illustrates theper-week proportion of subjects who had two additional CSBMs relative tothe baseline, for at least six out of eight weeks. Stated differently,for each week in FIGS. 6A and 6B, the value represents the percentage ofthe subjects who met the criteria (i.e. had one or two additional CSBMper week for six out of eight weeks) and who had an additional one ortwo CSBM on that specific week.

As is clearly evident from the results presented herein, more than 40%of the trial subjects experienced at least one additional CSBM per weekfor at least six out of the eight weeks. Furthermore, more than 23%experienced at least two additional CSBMs per week for at least six outof the eight weeks. The percentage of placebo subjects to experience thesame level of improvement is approximately half that of the trialsubjects, demonstrating the efficacy of the capsules.

Additionally, as discussed hereinabove, in Example 2 the percentage ofsubjects who experienced additional CSBMs is approximately 15%, ascompared to the results of Example 3 in which the percentage of trialsubjects who experienced additional CSBMs is greater than 23%. This isindicative of vibration during lunchtime and suppertime being moreefficacious than vibration during breakfast time and lunchtime, andsupports the Applicant's understanding regarding therapeutic windows forproviding vibration.

Further, as discussed hereinabove, in Example 2 each capsule vibratedtwice, i.e. for a single day. As a result, no two capsules werevibrating simultaneously in different parts of the GI tract. Bycontrast, in Example 3, two, and in some cases even three, capsules werevibrating concomitantly in different parts of the GI tract. As such, thedifference in results between Examples 2 and 3 may indicate an advantagein providing simultaneous vibration by multiple capsules in differentportions of the GI tract.

Comparison of the results of Examples 2 and 3 indicates that there areone or more better times for operation of vibrating capsules accordingto the present invention. Such better times may be during times in whichthe digestive system is active, e.g. during mealtime, but not duringtimes that the gastrointestinal tract is sufficiently active withcontractions suitable for generating an SBM or CSBM.

Without wishing to be bound by theory, the Applicants surmise that whenthe gastrointestinal tract is sufficiently active with contractionssuitable for generating an SBM or a CSBM, such as during the morninghours or during breakfast time, any impact of the vibrations of thecapsule is small, or even negligible, relative to the contractionsalready occurring. The Applicants further surmise that when thedigestive system is inactive, for example not during mealtimes,vibrations of the capsule are insufficient to generate peristalticactivity of the gastrointestinal tract. However, when the digestivesystem is active, but typically not active enough to generate a bowelmovement, activation of the vibrating capsule may “assist” thegastrointestinal tract in completing a bowel movement, resulting in anincrease in the number of bowel movements the user experiences during apredefined duration, e.g. per week.

The results of the study with respect to straining are further shown inFIG. 6C. FIG. 6C illustrates the per-week proportion of subjects whoexperienced an improvement in straining (i.e. reduction of strainingduring defecating) of at least 3 points in an 11 point scale. Stateddifferently, for each week in FIG. 6C, the value represents thepercentage of the subjects who met the criteria (i.e. had an improvementin straining of at least 3 points in the 11 point scale) and whoexperienced that improvement on that specific week.

As seen in FIG. 6C, during all eight weeks of the trial, the proportionof trial subjects who experienced an improvement of at least 3 points instraining is greater than the proportion of placebo subjects whoexperienced the same level of improvement. As seen, in at least six ofthe eight weeks of the trial, more than 30% of the trial subjectsexperienced an improvement in straining.

The results of the study with respect to stool consistency are furthershown in FIG. 6D. FIG. 6D illustrates the per-week proportion ofsubjects who experienced an improvement in stool consistency (i.e. anincrease in the Bristol stool score of defecations) of at least 1 pointsin the point Bristol stool scale. Stated differently, for each week inFIG. 6D, the value represents the percentage of the subjects who met thecriteria (i.e. had an increase of at least 1 point in the Bristol stoolscore) and who experienced that improvement on that specific week.

As seen in FIG. 6D, during all eight weeks of the trial, the proportionof trial subjects who experienced an improvement of at least 1 points inthe Bristol stool score is greater than the proportion of placebosubjects who experienced the same level of improvement. As seen, sevenof the eight weeks of the trial, more than 40% of the trial subjectsexperienced an improvement in stool consistency, and in five of theeight weeks more than 50% of the trial subjects experienced animprovement in stool consistency.

As such, it is clearly evident that in addition to improving the numberof CSBMs of the subjects, the treatment protocol used in Example 3 isalso successful in improving subjects' need for straining, and improvingBristol stool scores, for many of the trial subjects.

In some cases, the increase in the number of weekly bowel movements,together with improvement in the straining and/or stool consistencyparameters, was sufficient to remove some subjects from the Rome IIIcriteria or other criteria used to identify the clinical definition ofchronic constipation severity, thereby not only improving thesesubjects' symptoms, but also improving their diagnosis.

It will be appreciated that certain features of the invention, whichare, for clarity, described in the context of separate embodiments, mayalso be provided in combination in a single embodiment. Conversely,various features of the invention, which are, for brevity, described inthe context of a single embodiment, may also be provided separately orin any suitable sub-combination.

Although the invention has been described in conjunction with specificembodiments thereof, it is evident that many alternatives, modificationsand variations will be apparent to those skilled in the art.Accordingly, it is intended to embrace all such alternatives,modifications and variations that fall within the spirit and broad scopeof the appended claims. All publications, patents and patentapplications mentioned in this specification are herein incorporated intheir entirety by reference into the specification, to the same extentas if each individual publication, patent or patent application wasspecifically and individually indicated to be incorporated herein byreference. In addition, citation or identification of any reference inthis application shall not be construed as an admission that suchreference is available as prior art to the present invention.

1. A gastrointestinal capsule for mitigating at least one jetlag symptomof a subject travelling from an origin location to a destinationlocation, the gastrointestinal capsule being adapted for vibrating in agastrointestinal tract of the subject said gastrointestinal capsulecomprising: (a) a housing (b) a vibrating agitator adapted such that, ina first vibrating mode of operation, said housing exerts vibrations onan environment surrounding said gastrointestinal capsule; (c) a powersupply disposed within said housing and adapted to power said vibratingagitator; and (d) a controller adapted, in response to receipt of anactivation input, to activate said vibrating agitator to operate in saidfirst vibrating mode of operation at at least one predetermined time ofday, said at least one predetermined time of day being computedaccording to a time zone of the origin location or according to a timezone of the destination location.
 2. The gastrointestinal capsule ofclaim 1, wherein said at least one predetermined time of day is selectedaccording to a circadian cycle of the subject.
 3. The gastrointestinalcapsule of claim 1, wherein said at least one predetermined time of dayis a time of day coinciding with at least one mealtime in said time zoneof the origin location or in said time zone of the destination location.4. (canceled)
 5. The gastrointestinal capsule of claim 3, wherein saidat least one mealtime is a region-specific mealtime in said time zone ofthe origin location or in said time zone of the destination location. 6.The gastrointestinal capsule of claim 1, wherein said at least onepredetermined time of day is computed according to the time zone of theorigin location.
 7. The gastrointestinal capsule of claim 1, wherein theat least one predetermined time of day is computed according to the timezone of the destination location. 8-9. (canceled)
 10. A method ofmitigating at least one symptom of jetlag of a subject travelling froman origin location to a destination location, the method comprising: (a)providing to the subject a gastrointestinal capsule according to claim1; (b) following introduction of said gastrointestinal capsule to thegastrointestinal tract of the subject, and when said gastrointestinalcapsule is in an operative state, activating said vibrating agitator tooperate in said first vibrating mode of operation at at least onepredetermined time of day, said at least one predetermined time of daybeing computed according to a time zone of the origin location oraccording to a time zone of the destination location; and (c) repeatingsteps (a) and (b), which together form a treatment session, one to seventimes per week, thereby to mitigate the at least one symptom of jetlagof the subject.
 11. The method of claim 10, further comprising receivinginput relating to a circadian cycle of the subject, and said at leastone predetermined time of day is selected according to the circadiancycle of the subject.
 12. The method of claim 10, wherein said at leastone predetermined time of day is a mealtime. 13-17. (canceled)
 18. Themethod of claim 10, wherein said activating of said vibrating agitatorcomprises activating said vibrating agitator to operate in said firstvibrating mode of operation for a predetermined duration at eachactivation thereof.
 19. The method of claim 10, said repeating saidsteps (a) and (b) one to seven times per week comprises repeating saidsteps (a) and (b) on two consecutive days such that first and secondsaid gastrointestinal capsules are disposed in two different locationswithin the gastrointestinal tract of the subject simultaneously, andsaid activating said vibrating agitator to operate in said firstvibrating mode of operation at said at least one predetermined time ofday on two consecutive days comprises activating said vibratingagitators of said first and second gastrointestinal capsules to operatein said first vibrating mode of operation, simultaneously at said twodifferent locations, during said at least one predetermined time of day.20. (canceled)
 21. The gastrointestinal capsule of claim 1, wherein saidat least one predetermined time of day comprises a first predeterminedtime of day and a second predetermined time of day, and wherein saidcontroller is adapted to activate said vibrating agitator to operate insaid first vibration mode of operation at said first predetermined timeof day according to said time zone of the origin location and at saidsecond predetermined time of day according to said time zone of thedestination location.
 22. The gastrointestinal capsule of claim 1,further comprising at least one location sensor adapted to identify ageographical region in which said gastrointestinal capsule is located,such that said at least one predetermined time of day coincides with atleast one region-specific mealtime of said geographical region.
 23. Agastrointestinal system for mitigating at least one jetlag symptom of asubject travelling from an origin location to a destination location,the gastrointestinal system comprising: a gastrointestinal capsuleaccording to claim 1; and a control unit adapted to provide saidactivation input to said controller of said gastrointestinal capsule,wherein said control unit comprises at least one location sensor adaptedto identify a geographical region in which said control unit is locatedor said gastrointestinal capsule is located, such that said control unitprovides said activation input so that said vibrating mode of operationoccurs at at least one predetermined time of day, which coincides withat least one region-specific mealtime of said geographical region. 24.The method of claim 10, wherein the at least one symptom of jetlagcomprises acute constipation.